A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient's own tumor cells, providing the widest cancer-specific antigen repertoire and a standardized, sustained, local delivery over days of a potent adjuvant achieved by encapsulated cell technology. We conducted an open-label, single-arm, first-in-human phase I study with MVX-ONCO-1 in patients with advanced refractory solid cancer. MVX-ONCO-1 comprises irradiated autologous tumor cells coimplanted with two macrocapsules containing genetically engineered cells producing granulocyte-macrophage colony-stimulating factor. Patients received six immunizations over 9 weeks without maintenance therapy. Primary objectives were safety, tolerability, and feasibility, whereas secondary objectives focused on efficacy and immune monitoring. Data from 34 patients demonstrated safety and feasibility with minor issues. Adverse events included one serious adverse event possibly related to investigational medicinal product and two moderate-related adverse events. More than 50% of the patients with advanced and mainly nonimmunogenic tumors showed clinical benefits, including partial responses, stable diseases, and prolonged survival. In recurrent/metastatic head and neck squamous cell carcinoma, one patient achieved a partial response, whereas another survived for more than 7 years without anticancer therapy for over 5 years. MVX-ONCO-1 is safe, well tolerated, and beneficial across several tumor types. Ongoing phase IIa trials target patients with advanced recurrent/metastatic head and neck squamous cell carcinoma after initial systemic therapy. SIGNIFICANCE: This first-in-human phase I study introduces a groundbreaking approach to personalized cancer immunotherapy, addressing limitations of traditional strategies. By combining autologous irradiated tumor cells as a source of patient-specific antigens and utilizing encapsulated cell technology for localized, sustained delivery of granulocyte-macrophage colony-stimulating factor as an adjuvant, the study shows a very good safety and feasibility profile. This innovative approach holds the promise of addressing tumor heterogeneity by taking advantage of each patient's antigenic repertoire.

Supervivencia libre de progresión en pacientes portadores de meningiomas vacunados con nimotuzumab / Progression free survival in patients with meningioma which got Nimotuzumab vaccine

Introducción: en los últimos años la biología de los meningiomas cerebrales ha comenzado a entenderse mejor. La inmunoterapia activa contra el factor de crecimiento epidérmico es un concepto emergente, en el que se propone manipular la respuesta inmune del individuo, para generar anticuerpos específicos contra el factor de crecimiento epidérmico, capaces de bloquear la unión ligando-receptor y por consiguiente la señalización a través de este último. El receptor del factor de crecimiento epidérmico está sobrexpresado en este tipo de tumor. Objetivo: estimar la sobrevida libre de progresión de la entidad clínica y su relación con algunas variables socio-demográficas y terapéuticas seleccionadas. Métodos: se realizó un estudio descriptivo, transversal, en 25 pacientes portadores de meningiomas, tratados con un anticuerpo monoclonal humanizado (AcM h-R3) (nimotuzumab), en el Hospital Provincial Docente Clínico Quirúrgico Saturnino Lora de Santiago de Cuba, en el período comprendido entre el 1 de diciembre del 2013 y el 30 de noviembre del 2015. Resultados: el conjunto de pacientes incluidos en el estudio (n= 25) se caracterizó por el predominio del sexo femenino (60 por ciento), edad de 50 y más años (68 por ciento), piel blanca (48 por ciento) y escala de Karnofsky de 100 puntos (84 por ciento). El tiempo medio libre de progresión fue de 17 ± 8,6 meses. Conclusiones: fueron identificadas las principales características de la supervivencia libre de progresión del meningiomas en pacientes vacunados con AcM h-R3 y el tiempo fue como promedio de alrededor de año y medio(AU)

Introduction: in recent years the biology of brain meningiomas has begun to be better understood. Active immunotherapy against epidermal growth factor is an emerging concept, in which it is proposed to manipulate the immune response of the individual, to generate specific antibodies against epidermal growth factor, capable of blocking the ligand / receptor binding and therefore signaling through the latter. The epidermal growth factor receptor is overexpressed in this type of tumor. Objective: to estimate the progression free survival and its relation with some selected socio-demographic and therapeutic variables. Methods: a descriptive, cross-sectional study was conducted in 25 patients with meningiomas, treated with a humanized monoclonal antibody (mAb h-R3) (Nimotuzumab), in the Provincial Clinical-Surgical Teaching Hospital Saturnino Lora of Santiago de Cuba, from December 1, 2013 to November 30, 2015. Results: the group of patients included in the study (n= 25), was characterized by the predominance of females (60 percent), age 50 and over (68 percent), white skin (48 percent) and Karnofsky scale of 100 points (84 percent). The mean progression-free time was 17 ± 8.6 months. Conclusions: the main characteristics of progression-free survival of meningiomas were identified in patients vaccinated with mAb h-R3 and the progression-free time reached almost of a year and a half(AU)

Histopathological and immunohistochemical aspects of American cutaneous leishmaniasis before and after different treatments* / Aspectos histopatológicos e imuno-histoquímicos da leishmaniose tegumentar americana antes e depois de diferentes tratamentos

The histopathology and immune responses of the healing process of leishmaniasis are still poorly studied. This study aimed to examine the histopathological and immunological aspects of lesions of patients with cutaneous leishmaniasis before and after different therapeutic methods. We studied 23 individuals grouped according to the treatments: Glucantime, Glucantime + Leishvacin and Glucantime + Leishvacin associated with Bacillus Calmette-Guerin. For analysis of the histopathological changes present in the dermis and epidermis, histological sections were stained with hematoxylin and eosin. The samples were immunostained before and after treatment to analyze the expression of interferon (IFN)-γ, interleukin (IL) 12, IL-10 and IL-4. Before treatment the presence of intense infiltrates of mononuclear cells was noticed and after treatment, even with a diagnosis of clinical cure, the subjects still showed a moderate inflammatory process. In the immunohistochemical analyses, we noticed a difference between the cytokines, with increased expression of cytokines IFN-γ and IL-12 compared to IL 10 and IL-4, both before and after treatment and, comparatively, the difference in this expression was more intense before treatment. However, the cytokine expression analyzed by treatment group showed no statistically significant difference. We conclude that a clinical cure does not always coincide with the histopathological ...

A histopatologia e as respostas imunológicas do processo de cura da leishmaniose são ainda pouco estudadas. Este estudo teve como objetivo avaliar os aspectos histopatológicos e imunológicos das lesões de pacientes com leishmaniose tegumentar, antes e após diferentes métodos terapêuticos. Foram estudados 23 indivíduos agrupados de acordo com os tratamentos: Glucantime, Glucantime + Leishvacin e Glucantime + Leishvacin associado com Bacilo Calmette-Guerin. Para a análise das alterações histopatológicas presentes na derme e epiderme, cortes histológicos foram corados com hematoxilina e eosina. Para avaliar a expressão de interferon (IFN)-γ, interleucina (IL) 12, IL-10 e IL-4 foi utilizada a técnica de imuno-histoquímica antes e após o tratamento. Antes do tratamento houve um intenso infiltrado de células mononucleares, após o tratamento, mesmo com um diagnóstico de cura clínica, apresentou-se ainda um moderado processo inflamatório. Na análise imuno-histoquímica, notamos uma diferença entre as citocinas, com expressão aumentada de citocinas IFN-γ e IL-12 em comparação com IL-10 e IL-4 tanto antes quanto depois do tratamento, e comparativamente, a diferença nesta expressão mostrou-se mais intensa antes do tratamento. No entanto, a expressão das citocinas analisadas por grupo de tratamento não mostraram diferenças ...

Empleo de inmunoterapia en pacientes con infección producida por Staphylococcus aureus / Immunotherapy employment in patient with infection produced by Staphylococcus aureus

La infección cutánea por Staphylococcus aureus constituye en estos momentos un problema de salud en nuestra población, por su elevada frecuencia, resistencia a la terapia antibiótica y por sus complicaciones. Se realizó un ensayo clínico, fase II, controlado, abierto y aleatorizado, con el objetivo de demostrar el efecto terapéutico y seguridad de la autovacuna como tratamiento de la estafilococia. Se incluyeron 457 pacientes con diagnóstico de Staphylococcus aureus en lesiones de piel, y se dividieron en dos grupos. El grupo A (237 pacientes), recibió la aplicación de la autovacuna obtenida a partir del microorganismo aislado en cada sujeto, y el grupo B (220 pacientes), recibió tratamiento antibiótico según resultados del antibiograma. Con la aplicación de la autovacuna, se obtuvo un 82 por ciento de curación, y sólo el 10 por ciento de los pacientes tuvo reaparición de forúnculos en el intervalo de 6 meses posterior a la terminación del tratamiento. Sin embargo, con la aplicación de la antibioticoterapia se observó un 12 por ciento de curación y un 75 por ciento de reaparición de forúnculos en ese intervalo de tiempo. La autovacuna resultó ser más eficaz en el tratamiento de la infección bacteriana por Staphylococcus aureus que los antimicrobianos, además de ser una inmunoterapia bien tolerada por la mayoría de los paciente

The skin infection by Staphylococcus aureus is currently a health problem in our population, because of its high frequency, resistance to the antibiotic therapy and its complications. We carried out a randomized, open, controlled, phase II clinical trial, with the objective of demonstrating the therapeutic effect and safety of the autovaccine as a treatment of the Staphylococcus infections. 457 patients with a diagnosis of Staphylococcus aureus in skin lesions were included, and they were divided in two groups. Group A (237 patients), received the autovaccine obtained form the micro organism isolated in each subject, and group B (220 patients), received antibiotic treatment according to the antibiogram results. With the application of the autovaccine, we obtained 82 per cent of healing, and only 10 per cent of the patients had the reappearance of furuncles in an interval of 6 months after finishing the treatment. However, with the application of the antibiotic therapy there was 12 per cent of healing and 75 per cent of reappearance of the furuncles in the mentioned time interval. The autovaccine was more effective in the treatment of the bacterial infection by Staphylococcus aureus that the antimicrobial agents besides being a good tolerated immunotherapy for most of the patients

Immunotherapy of melanoma: peptide mimics of a human high molecular weight-melanoma associated antigen

The realization that tumor cells utilize multiple mechanisms to escape from immune recognition and destruction has stimulated interest in developing and applying immunotherapeutic strategies which target both humoral and cellular immunity to malignant cells. As a result, the tumor-associated antigens (TAA) used as targets have to be expressed on the cell surface membrane of malignant cells. Furthermore, since most of the TAA used for active specific immunotherapy are self-antigens, a challenge facing tumor immunologists is to develop strategies which are effective in breaking tolerance to self-antigens. This chapter describes one strategy which relies on the use of peptide mimics of the human high molecular weight-melanoma associated antigen (HMW-MAA) as immunogens to implement active specific immunotherapy in patients with malignant melanoma. These mimics, which are isolated from phage display peptide libraries by panning with anti-HMW-MAA monoclonal antibodies, are expected to induce both humoral and cellular anti-HMW-MAA immunity.

Immunological properties of gene vaccines delivered by different routes

Gene vaccines represent a new and promising approach to control infectious diseases, inducing a protective immune response in the appropriate host. Several routes and methods of genetic immunization have been shown to induce antibody production as well as T helper (Th) cell and cytotoxic T lymphocyte activation. However, few studies have compared the nature of the immune responses generated by different gene vaccination delivery systems. In the present study we reviewed some aspects of immunity induced by gene immunization and compared the immune responses produced by intramuscular (im) DNA injection to gene gun-mediated DNA transfer into the skin of BALB/c mice. Using a reporter gene coding for ß-galactosidase, we have demonstrated that im injection raised a predominantly Th1 response with mostly IgG2a anti-ßgal produced, while gene gun immunization induced a mixed Th1/Th2 profile with a balanced production of IgG2a and IgG1 subclasses. Distinct types of immune responses were generated by different methods of gene delivery. These findings have important implications for genetic vaccine design. Firstly, a combination between these two systems may create optimal conditions for the induction of a broad-based immune response. Alternatively, a particular gene vaccine delivery method might be used according to the immune response required for host protection. Here, we describe the characteristics of the immune response induced by gene vaccination and the properties of DNA involved in this process