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1.
J Cancer Res Clin Oncol ; 150(7): 347, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990367

RESUMO

BACKGROUND: Therapeutic approach used for pancreatic ductal adenocarcinoma is usually translated also for the rarer acinar counterpart, which shows a different mutational landscape nevertheless. While dMMR/MSI-H status is rare in the ductal histotype, it appears to be more prevalent in pancreatic acinar cell carcinoma (PACC). CASE PRESENTATION: We report the case of a patient with locally advanced MSI-H PACC in whom the treatment with the anti-PD-1 pembrolizumab, administered as third line, made possible surgical resection, achieving even an exceptional pathological complete response. CONCLUSIONS: Treatment of PACC should be tailored based on the peculiar molecular features that distinguish PACC from ductal adenocarcinoma. Evaluation of potentially therapeutically targetable alterations should be mandatory in case of PACC diagnosis.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células Acinares , Neoplasias Pancreáticas , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Carcinoma de Células Acinares/tratamento farmacológico , Carcinoma de Células Acinares/patologia , Masculino , Antineoplásicos Imunológicos/uso terapêutico , Pessoa de Meia-Idade , Idoso
2.
Anticancer Drugs ; 35(7): 644-652, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950136

RESUMO

Cervical cancer is one of the most common malignant tumors in women, and more than one-third of the patients have already developed to a locally advanced stage at initial diagnosis. After standard concurrent chemoradiotherapy, recurrence still occurs in 29-38% of patients with locally advanced cervical cancer (LACC), and the 5-year survival rate of patients with recurrence is only 3.8-13.0%, resulting in a poor prognosis and limited therapeutic choices. Currently, the recommended first-line systemic treatment for recurrent metastatic cervical cancer involves cisplatin or carboplatin in combination with paclitaxel-based chemotherapy, supplemented with the antivascular agent bevacizumab and the immune checkpoint inhibitor pembrolizumab. The use of these drugs, however, is limited due to side effects such as myelosuppression, gastrointestinal perforation, and bleeding, so new treatment modalities need to be explored. Anti-EGFR (epithelial growth factor receptor, anti-surface growth factor receptor antibody) targeted drugs have been demonstrated to have a significant radiosensitizing effect on synchronous chemoradiotherapy in LACC and are now considered to have potential for the treatment of recurrent cervical cancer. We represented a LACC patient who relapsed 6 months after concurrent chemoradiotherapy. The patient received six cycles of nimotuzumab combined with camrelizumab, and the efficacy was evaluated to be partial remission after two or four cycles of treatment, with progression-free survival up to 9 months, without significant side effects. Until March 2024, the patient was still undergoing treatment. Promising efficacy and tolerable side effects of nimotuzumab in combination with camrelizumab were observed in this case.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Recidiva Local de Neoplasia , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Feminino , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Imunoterapia/métodos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem
3.
Front Immunol ; 15: 1398508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38983860

RESUMO

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs). Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems. Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice. Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.


Assuntos
ADP-Ribosil Ciclase 1 , Antígeno CD47 , Neoplasias Hematológicas , Antígeno CD47/imunologia , Antígeno CD47/antagonistas & inibidores , Antígeno CD47/metabolismo , ADP-Ribosil Ciclase 1/antagonistas & inibidores , ADP-Ribosil Ciclase 1/imunologia , ADP-Ribosil Ciclase 1/metabolismo , Humanos , Animais , Camundongos , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/imunologia , Linhagem Celular Tumoral , Anticorpos Biespecíficos/farmacologia , Anticorpos Biespecíficos/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/antagonistas & inibidores , Citotoxicidade Celular Dependente de Anticorpos , Feminino , Antineoplásicos Imunológicos/farmacologia
6.
Med Sci (Paris) ; 40(6-7): 569-572, 2024.
Artigo em Francês | MEDLINE | ID: mdl-38986105

RESUMO

Title: L'immunocytokine FAP-IL2v: Un co-traitement efficace pour pallier la résistance au trastuzumab du cancer du sein HER2. Abstract: Dans le cadre de leur module d'analyse scientifique, des étudiants des promotions 2022-2023 et 2023-2024 des Master 2 « Immunologie Translationnelle et Biothérapies ¼ (ITB) et « Immunologie Intégrative et Systémique ¼ (I2S) (Mention Biologie Moléculaire et Cellulaire, Parcours Immunologie, Sorbonne Université) se sont penchés sur la littérature et ont pris la plume pour partager avec les lecteurs de m/s quelques-uns des faits marquants de l'actualité en immunologie. Voici une sélection de quelques-unes de ces nouvelles, illustrant la large palette des axes de recherche en cours sur les mécanismes physiopathologiques des maladies infectieuses, auto-immunes, inflammatoires et tumorales et sur le développement d'immunothérapies pour le traitement de ces pathologies. On y découvre ainsi de nouvelles avancées sur l'analyse transcriptomique du microenvironnement inflammatoire de pathologies autoimmunes, sur des aspects mécanistiques impliqués dans la survie des cellules cancéreuses et la réponse immunitaire anti-tumorale des cellules NK, l'interconnexion entre le système immunitaire et le système nerveux périphérique, le développement de nouvelles immunothérapies permettant de cibler préférentiellement le microenvironnement tumoral et la prise en charge des effets secondaires autoimmuns cardiaques induits par les immunothérapies. Toute l'équipe pédagogique remercie également chaleureusement les différents tuteurs, experts dans le domaine en lien avec les nouvelles, qui ont accompagné avec bienveillance et enthousiasme le travail de nos étudiants !


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Receptor ErbB-2 , Trastuzumab , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Receptor ErbB-2/antagonistas & inibidores , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Trastuzumab/uso terapêutico , Imunoterapia/métodos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
7.
BMC Pulm Med ; 24(1): 327, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977996

RESUMO

BACKGROUND: Adverse events of secondary adrenal insufficiency caused by anti-PD-1 immune agents are relatively rare in clinical practice, so in this article, we retrospectively analyzed three patients who suffered secondary adrenal cortex dysfunction caused by tislelizumab immunotherapy for Non-Small Cell Lung Cancer (NSCLC)and reviewed the literature. This rare immune-related adverse event was investigated by summarizing the clinical features of the patients. CASE PRESENTATION: We reported three NSCLC patients who suffered secondary adrenal cortex dysfunction induced by tislelizumab immunotherapy at our hospital from July 2021 to October 2023. We analyzed and summarized the clinical characteristic, laboratory examination, pathological staging, etc. We also reviewed related literature of pituitary inflammation and adrenal cortex dysfunction caused by immunotherapy. RESULTS: The median age of the three patients was 56 years. All the patients had a history of smoking. After receiving tislelizumab treatment (median cycle: 7), laboratory examination showed a decrease in morning cortisol and adrenocorticotropic hormone (ACTH), both were diagnosed with secondary adrenal insufficiency. Only one patient had symptoms of fatigue, vomiting, and weight loss. One of these patients also had simultaneous subclinical hypothyroidism. All three patients discontinued immunotherapy and received replacement therapy with glucocorticoids. At the last follow-up, none of the three patients restarted immunotherapy, because cortisol did not return to normal. This is similar to that of previous reports. CONCLUSION: Based on previous reports and our three cases, when laboratory tests of NSCLC patients receiving immunotherapy showed a decrease in morning cortisol and ACTH levels, especially when clinical symptoms were obvious, the possibility of immunotherapy-related pituitary inflammation causing secondary adrenal cortex dysfunction should be considered. Prompt monitoring and hormone replacement therapy should be provided to prevent adrenal crises.


Assuntos
Insuficiência Adrenal , Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Masculino , Insuficiência Adrenal/induzido quimicamente , Feminino , Imunoterapia/efeitos adversos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Antineoplásicos Imunológicos/efeitos adversos , Estudos Retrospectivos , Idoso , Hormônio Adrenocorticotrópico
8.
Cancer Biol Ther ; 25(1): 2373497, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38967961

RESUMO

Despite advances in targeted therapies, primary and acquired resistance make the treatment of colorectal cancer (CRC) a pressing issue to be resolved. According to reports, the development of CRC is linked to miRNA dysregulation. Multiple studies have demonstrated that miR-135b-5p has an aberrant expression level between CRC tissues and adjacent tissues. However, it is unclear whether there is a correlation between miR-135b-5p and cetuximab (CTx) resistance in CRC. Use the GEO database to measure miR-135b-5p expression in CRC. Additionally, RT-qPCR was applied to ascertain the production level of miR-135b-5p in three human CRC cells and NCM460 cells. The capacity of cells to migrate and invade was examined utilizing the wound-healing and transwell assays, while the CCK-8 assay served for evaluating cell viability, as well as colony formation assays for proliferation. The expected target protein of miR-135b-5p in CRC cell cetuximab resistance has been investigated using western blot. Suppression of miR-135b-5p could increase the CTx sensitivity of CTx-resistant CRC cells, as manifested by the attenuation of proliferation, migration, and invasion ability. Mechanistic studies revealed miR-135b-5p regulates the epithelial-to-mesenchymal transition (EMT) process and Wnt/ß-catenin signaling pathway through downgulating FOXN3. In short, knockdowning miR-135b-5p could increase FOXN3 expression in CRC cells, promote the EMT process, and simultaneously activate the Wnt/ß-catenin signaling pathway to elevate CTx resistance in CRC cells.


Assuntos
Cetuximab , Neoplasias Colorretais , Resistencia a Medicamentos Antineoplásicos , Fatores de Transcrição Forkhead , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Cetuximab/farmacologia , Cetuximab/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Proliferação de Células/efeitos dos fármacos , Movimento Celular , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Via de Sinalização Wnt/efeitos dos fármacos , Proteínas de Ciclo Celular
9.
Cancer Immunol Immunother ; 73(9): 161, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954006

RESUMO

BACKGROUND: Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment. MATERIALS AND METHODS: A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses. RESULTS: A total of 571 patients with a median age of 61 years (range 17-85) were included in the analysis. With a median follow-up of 22.1 (1.0-89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p < 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders. CONCLUSION: This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nivolumabe , Humanos , Nivolumabe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Adulto Jovem , Adolescente , Antineoplásicos Imunológicos/uso terapêutico , Seguimentos
10.
J Cardiothorac Surg ; 19(1): 421, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965530

RESUMO

BACKGROUND: Durvalumab supplementation may have some potential in improving the efficacy in patients with non-small-cell lung cancer (NSCLC), and this meta-analysis aims to explore the impact of durvalumab supplementation on efficacy for NSCLC. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of durvalumab supplementation on efficacy in patients with NSCLC. Overall survival and progression-free survival were included for this meta-analysis. RESULTS: Four RCTs were finally included in the meta-analysis. Overall, compared with control group for NSCLC, durvalumab supplementation showed significantly improved survival rate (odd ratio [OR] = 1.64; 95% confidence interval [CI] = 1.31 to 2.06; P < 0.0001), overall survival ( hazard ratio [HR] = 0.73; 95% CI = 0.61 to 0.87; P = 0.0003), progression-free survival rate (OR = 2.31; 95% CI = 1.78 to 3.01; P < 0.00001) and progression-free survival (HR = 0.71; 95% CI = 0.54 to 0.95; P = 0.02), and had the capability to reduce the incidence of grade ≥ 3 adverse events (OR = 0.26; 95% CI = 0.16 to 0.42; P < 0.00001). CONCLUSIONS: Durvalumab supplementation is effective to improve the efficacy for NSCLC.


Assuntos
Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Hinyokika Kiyo ; 70(4): 93-99, 2024 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-38965908

RESUMO

Small cell carcinoma of the bladder (SCCB) is a rare cancer that accounts for approximately 1% of primary malignant bladder tumors. It is highly malignant and has a poor prognosis. Similar to small cell lung cancer, platinum-based chemotherapy is recommended as the first-line therapy, and amrubicin (AMR) is recommended as the second-line therapy, but there is no established therapy after the second line. We report a case of SCCB that was refractory to multiple chemotherapies but responded to pembrolizumab. A 77-year-old male, diagnosed with clinical stage T3N0M0 small cell carcinoma and invasive urothelial carcinoma by transurethral resection of bladder tumor (TURBT), underwent robot-assisted radical cystectomy after three cycles of neoadjuvant cisplatin-irinotecan chemotherapy, and pathological examination revealed only small cell carcinoma in his cystectomy specimen. After three courses of adjuvant carboplatin-etoposide chemotherapy, the patient developed liver and bone metastases. Furthermore, after two courses of amrubicin, we started pembrolizumab due to the progression of metastases. Metastases decreased after starting pembrolizumab and continued to decrease after discontinuation because of immunerelated adverse events (irAEs). Therefore, pembrolizumab may be an option for the treatment of refractory SCCB.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células Pequenas , Neoplasias da Bexiga Urinária , Humanos , Masculino , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/cirurgia , Carcinoma de Células Pequenas/diagnóstico por imagem , Resultado do Tratamento , Antineoplásicos Imunológicos/uso terapêutico , Cistectomia
14.
Crit Rev Oncog ; 29(4): 43-54, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989737

RESUMO

Breast cancer (BC) is the most common cancer and the second leading cause of cancer-related deaths in women globally. Despite advancements in treatment strategies, many patients still develop challenging-to-treat metastatic disease. The development and progression of tumors are influenced by genetic/epigenetic changes within tumor cells and alterations in the tumor microenvironment (TME) through a dynamic communication. The TME comprises various elements, including immune, tumor, and stromal cells. Tumor cells at the core of the TME orchestrate complex signals that lead to tumor growth, survival, and resistance to treatment. Human epidermal growth factor receptor 2 (HER2) is overexpressed in a significant proportion of invasive breast cancers, influencing prognosis and prediction. Novel therapeutic approaches target HER2-positive breast cancers by leveraging HER2-targeted therapeuirtcs such as antibody-drug conjugates, monoclonal antibodies, and tyrosine kinase inhibitors. The TME in HER2-positive breast cancers also involves cancer-associated fibroblasts and cancer-associated adipocytes, which play critical roles in tumor progression and therapy resistance. The immune microenvironment also plays a significant role, with studies indicating its impact on outcomes in HER2-positive breast cancer. Trastuzumab, one of the first monoclonal antibodies targeting HER2, has shown promise in enhancing survival rates in HER2-overexpressing breast cancer. Integration of trastuzumab with chemotherapy has demonstrated significant enhancements in disease-free survival as well as overall survival rates during early breast cancer treatment. Trastuzumab functions by inhibiting HER2 signaling pathways, leading to cell cycle arrest and induction of apoptosis. Overall, understanding the complex interplay between HER2, the tumor microenvironment, and therapeutic interventions is essential for improving outcomes in HER2-positive BC.


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Receptor ErbB-2 , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Receptor ErbB-2/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Animais
15.
Acta Med Acad ; 53(1): 46-58, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38984699

RESUMO

OBJECTIVE: This systematic review aimed to compare the efficacy and safety of regorafenib and nivolumab, two FDA-approved second-line treatments for unresectable Hepatocellular Carcinoma (HCC). METHODS: Literature comparing the efficacy and safety of regorafenib and nivolumab in unresectable HCC patients was systematically searched across seven databases, including: PubMed, SCOPUS, Cochrane Database of Systematic Reviews, ScienceDirect, EBSCOhost, EMBASE, and ProQuest, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The search was done on April 2nd, 2023. Study quality and risk of bias were assessed using the Agency for Healthcare Research and Quality (AHRQ) and ROBINS-1 tools. The selected studies were included in the qualitative data synthesis. RESULTS: Three trials found that HCC patients taking nivolumab had statistically insignificantly longer OS, TTP, and progression-free survival than those on regorafenib. Nivolumab increased ORR, with largely partial responses, and mixed DCR, with little statistical significance. All three studies showed that nivolumab had fewer side effects and improved tolerance. DISCUSSION: Three retrospective cohort studies with a total of 383 regorafenib-receiving cohorts and 230 nivolumab-receiving cohorts were included in the qualitative analysis. Nivolumab was found to be superior in regards of longer overall survival, longer time to progression, higher objective response rate, and lower adverse event occurrence. However, statistical significance was not achieved in most of the parameters. CONCLUSIONS: The use of nivolumab is preferable as the second-line systemic therapy for unresectable HCC. More high-quality studies are urgently needed to generate quantitative analysis, and to encourage the formation of guidelines for second-line systemic therapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nivolumabe , Compostos de Fenilureia , Piridinas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos
16.
BMJ Case Rep ; 17(7)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38991576

RESUMO

Systemic capillary leak syndrome (SCLS) is a rare and life-threatening disorder characterised by leaking of intravascular fluid to extravascular tissues. An association with immunotherapy and COVID-19 vaccination has been reported as potential triggers. A case of a patient in her 70s developing SCLS after the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccination with a history of metastatic melanoma treated with nivolumab (PD-1 monoclonal antibody) and ipilimumab (anti-CTLA4 monoclonal antibody) is reported. The aetiology and management of SCLS are also reviewed in this case context.


Assuntos
COVID-19 , Síndrome de Vazamento Capilar , Ipilimumab , Melanoma , Nivolumabe , Humanos , Melanoma/tratamento farmacológico , Síndrome de Vazamento Capilar/induzido quimicamente , Nivolumabe/efeitos adversos , Feminino , Ipilimumab/efeitos adversos , Idoso , COVID-19/complicações , Vacinas contra COVID-19/efeitos adversos , Vacina BNT162/efeitos adversos , SARS-CoV-2 , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico
17.
Front Immunol ; 15: 1400177, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953027

RESUMO

Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs. Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods. Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model. Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.


Assuntos
Neoplasias , Receptores de IgG , Linfócitos T , Microambiente Tumoral , Receptores de IgG/imunologia , Receptores de IgG/metabolismo , Humanos , Animais , Camundongos , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Linfócitos T/imunologia , Microambiente Tumoral/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/imunologia , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Imunoterapia Adotiva/métodos , Receptor ErbB-2/imunologia , Receptor ErbB-2/antagonistas & inibidores , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Feminino , Antígenos CD20/imunologia
18.
J Cell Mol Med ; 28(13): e18470, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38963257

RESUMO

Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of rituximab as the first monoclonal antibody (mAb) for cancer treatment, several mAbs and antibody (Ab)-based therapies have been approved for the treatment of solid tumour malignancies and other cancers. These Abs function by either blocking oncogenic pathways or angiogenesis, modulating immune response, or by delivering a conjugated drug. The use of Ab-based therapy in cancer patients who could benefit from the treatment, however, is still limited by associated toxicity profiles which may stem from biological features and processes related to target binding, alongside biochemical and/or biophysical characteristics of the therapeutic Ab. A significant immune-related adverse event (irAE) associated with Ab-based therapies is cytokine release syndrome (CRS), characterized by the development of fever, rash and even marked, life-threatening hypotension, and acute inflammation with secondary to systemic uncontrolled increase in a range of pro-inflammatory cytokines. Here, we review irAEs associated with specific classes of approved, Ab-based novel cancer immunotherapeutics, namely immune checkpoint (IC)-targeting Abs, bispecific Abs (BsAbs) and Ab-drug-conjugates (ADCs), highlighting the significance of harmonization in preclinical assay development for safety assessment of Ab-based biotherapeutics as an approach to support and refine clinical translation.


Assuntos
Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/uso terapêutico , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico
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