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1.
Journal of Experimental Hematology ; (6): 1574-1578, 2023.
Article in Chinese | WPRIM | ID: wpr-1010008

ABSTRACT

Daratumumab is the first CD38 monoclonal antibody drug approved for the treatment of patients with multiple myeloma. It can bind to CD38 expressed by tumor cells, inhibit tumor cell growth and induce myeloma cell apoptosis through a variety of immune-related mechanisms. Meanwhile, CD38 is also expressed in other cells, including regulatory T cells, regulatory B cells and myeloid-derived suppressor cells, which provides a theoretical basis for the treatment of hematological tumor diseases other than non-multiple myeloma diseases. This article reviews the research progress and application of this part.


Subject(s)
Humans , Multiple Myeloma/pathology , ADP-ribosyl Cyclase 1 , Antibodies, Monoclonal/pharmacology , Hematologic Neoplasms/drug therapy
2.
Frontiers of Medicine ; (4): 805-822, 2023.
Article in English | WPRIM | ID: wpr-1010820

ABSTRACT

Immunotherapies based on immune checkpoint blockade (ICB) have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade. To date, immune checkpoint inhibitors (ICIs) of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy. Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers, however, a large subset of refractory patients presents poor responsiveness to ICB therapy; and the underlying mechanism remains elusive. Recently, numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment (TME) with various products of metabolism, and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy. Nevertheless, a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance. Here, we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints (CTLA-4, PD-1, and PD-L1) to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.


Subject(s)
Humans , Antibodies, Monoclonal/pharmacology , B7-H1 Antigen/antagonists & inhibitors , CTLA-4 Antigen/antagonists & inhibitors , Immune Checkpoint Inhibitors/pharmacology , Neoplasms/drug therapy , Programmed Cell Death 1 Receptor , Tumor Microenvironment
3.
Frontiers of Medicine ; (4): 1170-1185, 2023.
Article in English | WPRIM | ID: wpr-1010819

ABSTRACT

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.


Subject(s)
Mice , Animals , Receptors, Tumor Necrosis Factor/physiology , Receptors, OX40 , Membrane Glycoproteins , Ligands , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents/pharmacology
4.
Chinese Journal of Hematology ; (12): 400-407, 2022.
Article in Chinese | WPRIM | ID: wpr-929627

ABSTRACT

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.


Subject(s)
Humans , Antibodies, Monoclonal/pharmacology , Graft vs Host Disease/metabolism , Hematopoietic Stem Cell Transplantation , Killer Cells, Natural , Retrospective Studies , Treatment Outcome
5.
Rev. Soc. Bras. Clín. Méd ; 18(1): 55-68, marco 2020.
Article in Portuguese | LILACS | ID: biblio-1361347

ABSTRACT

O objetivo deste estudo foi realizar o levantamento bibliográfico de artigos científicos e ensaios clínicos sobre a utilização de anticorpos monoclonais, imunomoduladores e anti-inflamatórios como possíveis alternativas terapêuticas para uso em pacientes com COVID-19, com ênfase nos mecanismos de ação e resultados de ensaios clínicos. Foram analisados artigos obtidos na base de dados MEDLINE® e ensaios clínicos disponíveis no site ClinicalTrials no período de 6 de abril a 6 de maio de 2020. Os ensaios realizados com os fármacos apresentados nesta revisão bibliográfica sugerem a viabilidade de uso de algumas dessas drogas como alternativas para tratamento da COVID-19. No entanto, observou-se que, em função do número reduzido de participantes dos estudos disponíveis, é indispensável a continuidade de pesquisas e dos ensaios clínicos com esses medicamentos, para estimar a eficácia dessas drogas no tratamento do SARS-CoV-2, contra o qual ainda não há terapia específica


The objective of this study was to carry out a bibliographic survey of scientific articles and current clinical trials on the use of monoclonal antibodies, immunomodulators, and anti-inflammatories as possible therapeutic alternatives for use in patients with COVID-19, highlighting their mechanisms of action and results of clinical trials. Articles from the MEDLINE® database and clinical trials available on the ClinicalTrials website were analyzedThe tests performed with the drugs presented in this bibliographic review suggest the feasibility of using some of these drugs as treatment alternatives for COVID-19. However, it was observed that the small samples evaluated in these tests make it imperative to proceed with research and clinical trials with these drugs to provide greater evidence of the effectiveness of these drugs in the treatment of the disease caused by SARS-CoV-2, for which there is no specific therapy so far.


Subject(s)
Humans , COVID-19/drug therapy , Immunologic Factors/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Efficacy , Clinical Trials as Topic , COVID-19/complications , COVID-19/physiopathology , COVID-19/immunology , Immunologic Factors/adverse effects , Immunologic Factors/immunology , Immunologic Factors/pharmacology , Anti-Inflammatory Agents/adverse effects , Anti-Inflammatory Agents/immunology , Anti-Inflammatory Agents/pharmacology , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology
6.
Acta cir. bras ; 32(12): 1006-1012, Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-886195

ABSTRACT

Abstract Purpose: To evaluate the efficacy of nivolumab and comparison with dacarbazine (DTIC) on peritoneal carcinomatosis of malignant melanoma in mouse model. Methods: Mouse skin melanoma cells was injected under the capsule of the peritoneal surface in the left side of the abdomen. On postoperative day ten, mouses randomised into three groups. Group 1: Control, Group 2: HIPEC (Hyperthermic intraperitoneal chemotherapy) with DTIC and Group 3: HIPEC with Nivolumab. After the sacrification on postoperative day fifteen, peritoneum evaluated macroscopically and histopathologically by using peritoneal regression grading score (PRGS). Results: In the 15th day exploration, all animals developed extensive intraperitoneal tumor growth in Group 1. In Group 2 and Group 3 median tumor size was 0.7±0.3cm and 0.3±0.2cm respectively (p: 0.023). Peritoneal carcinomatosis index (PCI) were significantly lower in Group 3 than other groups (p: 0.019). The lowest total tumor nodules in group 3 was 4 ± 2. The PGRS score was found significantly lower in Group 3 than other groups (p: 0.03). Lymphocytic response rate was found higher in the Group 3. Conclusions: It has been found that nivolumab significantly better than DTIC on peritoneal metastases of malign melanoma in mouse models. Nivolumab treatment gives promising results with pathological evidence in the treatment of metastatic disease of malignant melanoma.


Subject(s)
Animals , Male , Rats , Peritoneal Neoplasms/drug therapy , Peritoneum/pathology , Melanoma/drug therapy , Antibodies, Monoclonal/pharmacology , Antineoplastic Agents/pharmacology , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/secondary , Peritoneum/drug effects , Random Allocation , Regression Analysis , Dacarbazine/therapeutic use , Disease Models, Animal , Drug Evaluation, Preclinical , Neoplasm Grading , Nivolumab , Hyperthermia, Induced , Melanoma/secondary , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use
7.
Colomb. med ; 47(4): 203-212, Oct.-Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-952885

ABSTRACT

Abstract Alzheimer disease (AD) is the most prevalent form of dementia of adult-onset, characterized by progressive impairment in cognition and memory. There is no cure for the disease and the current treatments are only symptomatic. Drug discovery is an expensive and time-consuming process; in the last decade no new drugs have been found for AD despite the efforts of the scientific community and pharmaceutical companies. The Aβ immunotherapy is one of the most promising approaches to modify the course of AD. This therapeutic strategy uses synthetic peptides or monoclonal antibodies (mAb) to decrease the Aβ load in the brain and slow the progression of the disease. Therefore, this article will discuss the main aspects of AD neuropathogenesis, the classical pharmacologic treatment, as well as the active and passive immunization describing drug prototypes evaluated in different clinical trials.


Resumen La enfermedad de Alzheimer (EA) es la forma más frecuente de demencia de inicio en el adulto, caracterizada por un deterioro progresivo en la cognición y la memoria. No hay cura para la enfermedad y los tratamientos actuales son sólo sintomáticos. El descubrimiento de fármacos es un proceso costoso y que consume mucho tiempo; en la última década no se han encontrado nuevos fármacos para la EA a pesar de los esfuerzos de la comunidad científica y las compañías farmacéuticas. La inmunoterapia contra Aβ es uno de los enfoques más prometedores para modificar el curso de la EA. Esta estrategia terapéutica utiliza péptidos sintéticos o anticuerpos monoclonales (mAb) para disminuir la carga de Aβ en el cerebro y retardar la progresión de la enfermedad. Por lo tanto, este artículo discutirá los principales aspectos de la neuropatogénesis de la EA, el tratamiento farmacológico clásico, así como la inmunización activa y pasiva describiendo los prototipos de fármacos evaluados en diferentes ensayos clínicos.


Subject(s)
Humans , Amyloid beta-Peptides/immunology , Alzheimer Disease/therapy , Immunotherapy/methods , Peptides/therapeutic use , Peptides/pharmacology , Disease Progression , Alzheimer Disease/physiopathology , Alzheimer Disease/immunology , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/pharmacology
8.
Yonsei Medical Journal ; : 165-172, 2016.
Article in English | WPRIM | ID: wpr-186108

ABSTRACT

PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.


Subject(s)
Animals , Humans , Rats , Acetylcholine/metabolism , Alzheimer Disease , Antibodies, Monoclonal/pharmacology , Basal Forebrain/drug effects , Cholinergic Agents/administration & dosage , Cholinergic Neurons/drug effects , Fluorodeoxyglucose F18 , GABAergic Neurons/drug effects , Glucose/metabolism , Gyrus Cinguli/drug effects , Injections , Maze Learning , Motor Activity/physiology , Positron-Emission Tomography , Ribosome Inactivating Proteins, Type 1/pharmacology
9.
Mem. Inst. Oswaldo Cruz ; 110(2): 174-180, 04/2015. tab, graf
Article in English | LILACS | ID: lil-744480

ABSTRACT

Sandfly prevalence in the Kani tribe settlements of Western Ghats in India was investigated. A total of 1,279 sandflies comprising 17 species was obtained. Sandfly abundance showed a negative correlation (r = -0.97, p = 0.003) with increase in altitudinal ranges from 0-1,000 m. When sandfly samples were grouped according to landscape characteristics of the location, the estimated Shannon-Weiner index (H) and species richness index (S) were high and species evenness index (J) was low in settlements located at 0-300 m altitudinal range. On the contrary, the values of H and J were high, while S was low at 301-600 m altitudinal range. With further increase in altitude, species diversity, S and J were low. Though the relative abundance of sandflies decreased with increase in altitude, the influence of altitudinal variation could not be attributed to determine sandfly diversity, since the number of sampling units were not uniform at all the altitudinal gradients due to nonavailability of suitable resting shelters. Sandfly species showed great aggregation at 0-300 m altitude interval, where not only the number of settlements were maximum (n = 19), but also the environmental conditions favoured sandfly abundance due to the concentration of tribal settlements, human dwellings and his activities.


Subject(s)
Humans , Hodgkin Disease/therapy , Molecular Targeted Therapy , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , /antagonists & inhibitors , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Hodgkin Disease/metabolism , Immunotherapy, Adoptive , Signal Transduction/drug effects , Tumor Microenvironment/drug effects
10.
Rev. Col. Bras. Cir ; 38(4): 266-273, jul.-ago. 2011. ilus, tab
Article in Portuguese | LILACS | ID: lil-601069

ABSTRACT

OBJETIVO: Avaliar o efeito da terapia anti-TNF-α no tratamento de implantes endometriais no peritônio de ratas. MÉTODOS: Os implantes endometrióticos foram induzidos cirurgicamente em 120 ratas Wistar-Albino. Os animais foram aleatoriamente distribuídos em 4 grupos. O grupo C (n=36) recebeu uma injeção intraperitoneal de 0,2ml de solução salina. O grupo L (n=41) recebeu uma injeção subcutânea de 1mg/kg de leuprolide. O grupo I5 (n=20) recebeu uma injeção subcutânea de 5mg/kg de anticorpo monoclonal anti-fator de necrose tumoral (TNF) a (infliximab). O grupo I10 (n=20) recebeu uma injeção subcutânea de 10mg/kg de infliximab. As ratas foram sacrificadas após 21 dias para se avaliar o tamanho dos implantes e a expressão do TNF-α. RESULTADOS: O tratamento com leuprolide promoveu uma redução absoluta na área de superfície do implante comparado com o grupo C (+14mm vs. 0mm; p=0,013) e com o grupo I10 (+14mm vs. +5mm; p=0,018). Da mesma forma, uma redução percentual da area de superfície do implante foi observada comparando o grupo L com o grupo C (+33,3 por cento vs. 0 por cento; p=0,005) e com o grupo I10 (+33,3 por cento vs. +18,3 por cento; p=0,027). O tratamento com infliximab não foi capaz de diminuir a área de superfície do implante comparado com o grupo C. A expressão de TNF-α reduziu nos grupos L, I5 e I10 comparado com o grupo C (505,6µm² vs. 660,5µm² vs. 317,2µm² vs. 2519,3µm², respectivamente; p<0,001). CONCLUSÃO: A terapia anti-TNF-α reduziu a expressão de TNF-α nos implantes endometrióticos mas não reduziu a área de superfície da lesão.


OBJECTIVE: To evaluate the effect of anti-TNF-α in the treatment of endometrial implants in the peritoneum of rats. METHODS: Endometrial implants were surgically induced in 120 female Wistar-Albino rats. The animals were randomly divided into four groups. Group C (n = 36) received an intraperitoneal injection of 0.2 ml of saline. Group L (n = 41) received a subcutaneous injection of 1mg/kg of leuprolide. Group I5 (n = 20) received a subcutaneous injection of 5mg/kg of monoclonal anti-tumor necrosis factor (TNF) a (infliximab). Group I10 (n = 20) received a subcutaneous injection of 10mg/kg of infliximab. The rats were sacrificed after 21 days to assess the size of the implants and the expression of TNF. RESULTS: Treatment with leuprolide (group L) promoted an absolute reduction in the surface area of the implant when compared with group C (+14 mm vs. 0mm, p = 0.013) and group I10 (+14 mm vs. +5 Mm, p = 0.018). Likewise, a percentage reduction of surface area of the implant was observed comparing group L with group C (+33.3 percent vs. 0 percent, p = 0.005) and group I10 (+33.3 percent vs. +18.3 percent, p = 0.027). Treatment with infliximab was not able to decrease the surface area of the implants when compared with group C. The expression of TNF-α in groups L, I5 and I10 was lower than in group C (505.6 mm² vs. 660.5 mm² vs. 317.2 mm² vs. 2519.3 mm², respectively; p <0.001). CONCLUSION: The anti-TNF-α therapy reduced the expression of TNF-α in endometriotic implants, but did not reduce the surface area of the lesion.


Subject(s)
Animals , Female , Rats , Antibodies, Monoclonal/pharmacology , Endometrium/drug effects , Endometrium/transplantation , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Peritoneum/surgery , Rats, Wistar
11.
Rev. cuba. med. trop ; 63(2): 123-129, mayo.-ago. 2011.
Article in Spanish | LILACS | ID: lil-615548

ABSTRACT

Introducción: las frecuencias de recaídas y elevada letalidad de la criptococosis se mantienen altas, lo cual incentiva la búsqueda de nuevas estrategias terapéuticas. Objetivos: evaluar el efecto del anticuerpo monoclonal 4B3 sobre la infección criptocócica en ratones BALB/c. Métodos: se determinó la cinética de la concentración sérica del anticuerpo monoclonal para su administración intraperitoneal (500 µg), que fue medida por ELISA cuantitativo de doble anticuerpo. La capacidad protectora se observó mediante el registro de supervivencia de ratones BALB/c administrados con 500 µg de anticuerpo monoclonal 4B3 e inoculados con 2 x 10(2,2) células/mL de Cryptococcus neoformans, así como por evaluación de la diseminación de la levadura a los principales órganos diana. Se identificó el efecto del anticuerpo monoclonal 4B3 sobre la fagocitosis y lisis del microorganismo por células de la línea de macrófagos P338.D1. Resultados: la dosis empleada fue suficiente para mantener valores séricos elevados del 4B3 (38 µg/mL) durante al menos 46 d. Se determinó que el 4B3 no confiere protección, lo cual potencia la diseminación del microorganismo y disminuye el tiempo de vida de los animales. El ensayo de fagocitosis mostró que el anticuerpo evaluado incrementa la actividad fagocítica de los macrófagos sin lograr un efecto fungicida. Conclusiones: el anticuerpo monoclonal 4B3 estimula la fagocitosis de C. neoformans por macrófagos, pero sin efecto fungicida. Con ello favorece la diseminación de la levadura y disminuye el tiempo de vida de los ratones a la infección.


Introduction: frequent relapses and high lethality of criptococcosis has encouraged the search for new therapeutic strategies. Objectives: to evaluate the effect of the monoclonal antibody 4B3 on the cryptococcal infection in Balb/c mice. Methods: the kinetics in serum concentration of the studied monoclonal antibody was determined for intraperitoneal administration (500 µg) by quantitative sandwich ELISA. In order to assess its protective capability, were administered 500 µg of 4B3 and innoculated 2 x 10(2.2) cells/mL of Cryptococcus neoformans. The survival of mice was recorded and the yeast dissemination to the main target organs was evaluated. Macrophages P338.D1 cell lines were used to measure the effect of the monoclonal antibody 4B3 on the phagocytosis and lysis of the microorganism. Results: the used dose helped to keep high values (38 µg/m) of 4B3 in serum for at least 46 days. It was found that the monoclonal antibody does not give protection, which makes the microorganism dissemination possible, along with the reduction in the survival of mice. Finally, the phagocytosis test showed that 4B3 increased the phagocytic activity of macrophages without any fungicidal effect. Conclusions: the monoclonal antibody 4B3 stimulates C. neoformans phagocytosis by macrophages without fungicidal effect, thus favoring yeast dissemination and decreasing the survival of mice due to cryptococcal infection.


Subject(s)
Animals , Male , Mice , Antibodies, Monoclonal/pharmacology , Cryptococcosis , Cryptococcus neoformans/drug effects , Disease Models, Animal , Mice, Inbred BALB C
12.
Braz. j. pharm. sci ; 47(1): 31-38, Jan.-Mar. 2011. ilus, graf, tab
Article in English | LILACS | ID: lil-586522

ABSTRACT

Monoclonal antibodies represent the fastest growing class of biopharmaceutical products and have a host of applications in medical research, diagnosis, therapy, and basic science. The production of recombinant monoclonal antibodies has revolutionized the generation of immunoglobulins, and their use represents a strategic breakthrough, affecting the global pharmaceutical market for therapeutic proteins. In the present work, a review of scFv, and the number of related patents, has been carried out. The results show that several countries have scFv patents, most notably the United States, China and United Kingdom. The target of these scFv antibodies was also assessed and the results demonstrate that most are directed toward cancer therapy.


Anticorpos monoclonais representam a classe de maior crescimento em produtos de biofármacos e possuem várias aplicações em pesquisa médica, diagnóstico, terapias e ciência básica. A produção de anticorpos monoclonais recombinantes revolucionou a geração de imunoglobulinas e sua utilização implica em avanço estratégico, afetando o mercado farmacêutico global de proteínas terapêuticas. No presente trabalho, uma revisão sobre scFv e a relação do seu número de patentes foi analisada. Os resultados mostram que vários países apresentam patentes de scFv com destaque para os Estados Unidos, China e Reino Unido. Os alvos desses anticorpos também foram avaliados e as análises revelaram que a maioria é destinado a terapias contra o câncer.


Subject(s)
Antigens, Differentiation , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Biopharmaceutics/trends , Drug Synergism , Intellectual Property of Pharmaceutic Products and Process , Colony-Stimulating Factors
13.
Article in English | WPRIM | ID: wpr-131302

ABSTRACT

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-alpha, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-alpha have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-alpha, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.


Subject(s)
Animals , Humans , Antibodies, Monoclonal/pharmacology , Antigens, CD20/immunology , Drug Discovery , Immune System Diseases/drug therapy , Immunotherapy/trends , Molecular Targeted Therapy , Neoplasms/drug therapy , ErbB Receptors/immunology , Receptor, ErbB-2/immunology , Tumor Necrosis Factor-alpha/immunology , United States , United States Food and Drug Administration , Vascular Endothelial Growth Factor A/immunology
14.
Article in English | WPRIM | ID: wpr-131299

ABSTRACT

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-alpha, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-alpha have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-alpha, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.


Subject(s)
Animals , Humans , Antibodies, Monoclonal/pharmacology , Antigens, CD20/immunology , Drug Discovery , Immune System Diseases/drug therapy , Immunotherapy/trends , Molecular Targeted Therapy , Neoplasms/drug therapy , ErbB Receptors/immunology , Receptor, ErbB-2/immunology , Tumor Necrosis Factor-alpha/immunology , United States , United States Food and Drug Administration , Vascular Endothelial Growth Factor A/immunology
15.
Rev. cuba. hematol. inmunol. hemoter ; 26(3): 186-197, sep.-dic. 2010.
Article in Spanish | LILACS | ID: lil-584699

ABSTRACT

El rituximab integra la primera generación de anticuerpos monoclonales anti CD20 que se utiliza como terapia biológica en los síndromes linfoproliferativos crónicos de estirpe B, en enfermedades autoinmunes y en otras entidades donde hay proliferación de linfocitos B. Es un anticuerpo monoclonal quimérico murino/humano que se obtiene por ingeniería genética, con eficacia y seguridad probadas, y que se puede usar como monoterapia o combinado con quimioterapia. En esta revisión se exponen los antecedentes históricos, la farmacología y las perspectivas de este medicamento


The Rituximab tartrate is part of the first generation of anti-CD20 monoclonal antibodies used as biological therapy in stock 3 chronic lymphoproliferative syndromes, in autoimmune diseases, and in others entities where is present a B lymphocyte proliferation. It is a murine/human chimera monoclonal antibody obtained by genetic engineering, with a proven safety and effectiveness and that may be used as monotherapy or combined with chemotherapy. In present review are showed the historical backgrounds, the pharmacology and the perspectives of this drug


Subject(s)
Humans , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/history , Antibodies, Monoclonal/therapeutic use
16.
Indian J Biochem Biophys ; 2010 Aug; 47(4): 219-226
Article in English | IMSEAR | ID: sea-135269

ABSTRACT

The inflammatory bowel disease (IBD) is an idiopathic, immune-mediated and chronic intestinal condition. In the present study, the effect of Serarud (IMOD®), a novel natural drug with known immunomodulatory, anti-inflammatory and antioxidant properties was investigated in experimental colitis in rats and compared with the dexamethasone and infliximab. Immunologic colitis was induced by intracolonic administration of a mixture of trinitrobenzene sulfonic acid (TNBS) and absolute ethanol in male Wistar rats. Animals were divided into 6 groups of sham (normal group), control (vehicle-treated), positive control (dexamethasone 1 mg/kg/day given orally and infliximab 5 mg/kg/day given subcutaneously) and 3 Setarud-treated groups (13.3, 20, 30 mg/kg/day given intraperitoneally). The treatment continued for 14 consecutive days and then animals were decapitated on the day 15 and distal colons were removed for macroscopic, microscopic, and biochemical assays. Biochemical markers, including TNF-, IL-1, ferric reducing/antioxidant power (FRAP), myeloperoxidase (MPO) activity and thiobarbitoric acid-reactive substance (TBARS) were measured in the homogenate of colonic tissue. A remarkable reduction in macroscopic and histological damage scores was observed in the animals treated with Setarud. These findings were confirmed by decreased levels of TNF-, interleukin-1, MPO activity and TBARS, and raised levels of FRAP in the colon tissue. These observations confirmed the immunomodulatory, anti-inflammatory and antioxidant properties of Setarud in experimental colitis, which was comparable to those of dexamethasone and infliximab.


Subject(s)
Animals , Anti-Inflammatory Agents/pharmacology , Antibodies, Monoclonal/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Dexamethasone/pharmacology , Humans , Interleukin-1beta/metabolism , Male , Oxidative Stress , Peroxidase/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Rats , Rats, Wistar , Thiobarbituric Acid Reactive Substances/chemistry , Time Factors , Tumor Necrosis Factor-alpha/metabolism
17.
Indian J Cancer ; 2010 Jul-Sept; 47(3): 248-259
Article in English | IMSEAR | ID: sea-144347

ABSTRACT

Despite significant improvements in the treatment and outcomes of patients with squamous cell carcinoma of the head and neck (SCCHN) that have resulted from technological advances in radiation delivery and the use of cytotoxic chemotherapy, there is still a pressing need for novel therapies. In the last two decades, our understanding of the molecular biological basis of cancer has provided us with a new framework for developing specific targeted therapies. It is likely that the next wave of developments will include active small molecule inhibitors of epidermal growth factor receptor (EGFR) (and other members of the c-erbB family of receptors), antiangiogenic agents, and drugs that can increase proapoptotic signaling in cancer cells. As with cetuximab, it is most likely that these new agents will first find a niche in the context of combination regimens with standard anticancer therapeutics.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Apoptosis/drug effects , Biological Therapy/trends , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Chemotherapy, Adjuvant , Drug Discovery , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Humans , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , ErbB Receptors/antagonists & inhibitors
18.
SPJ-Saudi Pharmaceutical Journal. 2010; 18 (4): 257-259
in English | IMEMR | ID: emr-123483
19.
Article in English | WPRIM | ID: wpr-188010

ABSTRACT

Despite the prophylaxis and preemptive strategies using potent antiviral agents, cytomegalovirus (CMV) remains a major infectious cause of morbidity and mortality in allogeneic stem cell transplantation (SCT) recipients. Delayed immune reconstitution after SCT, such as cord blood and T-cell depleted SCT with the use of alemtuzumab, has been associated with an increased frequency of CMV disease as well as CMV reactivation. CMV disease involving central nervous system is an unusual presentation in the setting of SCT. We report a case of CMV ventriculoencephalitis after unrelated double cord blood SCT with an alemtuzumab-containing preparative regimen for Philadelphia-positive acute lymphoblastic leukemia.


Subject(s)
Humans , Male , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized , Antibodies, Neoplasm/pharmacology , Antineoplastic Agents/pharmacology , Cord Blood Stem Cell Transplantation/adverse effects , Cytomegalovirus/drug effects , Cytomegalovirus Infections/drug therapy , Encephalitis/etiology , Fatal Outcome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Transplantation Conditioning/methods
20.
Mem. Inst. Oswaldo Cruz ; 104(4): 644-648, July 2009. graf
Article in English | LILACS | ID: lil-523734

ABSTRACT

Paracoccidioides brasiliensis, a thermal dimorphic fungal pathogen, produces a melanin-like pigment in vitro and in vivo. We investigated the involvement of carbohydrates and monoclonal antibody to CD18, on phagocytosis inhibition, involving macrophage receptors and the resistance of melanized fungal cells to chemically generated nitric oxide (NO), reactive oxygen species (ROS), hypochlorite and H2O2. Our results demonstrate that melanized yeast cells were more resistant than nonmelanized yeast cells to chemically generated NO, ROS, hypochlorite and H2O2, in vitro. Phagocytosis of melanized yeast cells was virtually abolished when mannan, N-acetyl glucosamine and anti-CD18 antibody were added together in this system. Intratracheal infection of BALB/c mice, with melanized yeast cells, resulted in higher lung colony forming units, when compared to nonmelanized yeast cells. Therefore, melanin is a virulence factor of P. brasiliensis.


Subject(s)
Animals , Mice , Antifungal Agents/pharmacology , Macrophages/microbiology , Melanins/biosynthesis , Oxidants/pharmacology , Phagocytosis , Paracoccidioides/pathogenicity , Antibodies, Monoclonal/pharmacology , /drug effects , Carbohydrates/pharmacology , Mice, Inbred BALB C , Paracoccidioides/drug effects , Paracoccidioides/metabolism , Virulence Factors/physiology
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