ABSTRACT
BACKGROUND AND AIMS: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes. METHODS: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease. RESULTS: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease. CONCLUSION: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.
Subject(s)
Adenocarcinoma , Prostatic Neoplasms , Vaccines , Male , Humans , Gonadotropin-Releasing Hormone , Prostate-Specific Antigen , Prospective Studies , Prostate , Neoplasm Recurrence, Local , Immunization , Prostatic Neoplasms/therapy , Vaccination , Immunoglobulin G , Testosterone , Castration , Adenocarcinoma/therapy , Immunoglobulin MABSTRACT
La biotecnología, aunque tan antigua como la invención del vino y la fermentación de la cerveza por el hombre, tiene en los años 60 del siglo XX, un importante despegue con las técnicas de biología molecular y clonaje de genes foráneos en organismos unicelulares, y el surgimiento de los primeros medicamentos recombinantes. En la década de 1980 y 1990, se obtiene sorprendentes resultados de transgénesis de animales y plantas y ya finalizando el siglo aparece la clonación ó generación de animales idénticos a partir de células somáticas. En este trabajo se valora críticamente las oportunidades y riesgos de la transgénesis y la clonación en el plano ético actual, teniendo en cuenta la amenaza de los seres clónicos, la responsabilidad social de los científicos, la polarización del sistema científico internacional y los códigos morales, además de la ética del profesional científico cubano que responde al principio de que el futuro de nuestra patria tiene que ser necesariamente un futuro de hombres de ciencia (AU)
Even though Biotechnology is as old as the invention of wine and beer fermentation by men, it experiences an important take off in the 60s, with the development of molecular biology techniques and cloning of strange genes in unicellular organisms, and the emergence of the first recombinant medications. In the decade of 1980 and 1990, surprising results in transgenesis of animals and plants are obtained and by the end of the century cloning or generation of identical animals starting from somatic cells is carried out. In this work the opportunities and risks of transgenesis and cloning are analyzed critically taking into account the current ethical perspective, keeping in mind the threat of cloned beings, the social responsibility of scientists, the polarization of the international scientific system and moral codes, as well as the Cuban science professionals ' ethics that responds to the principle that the future of our homeland is necessarily a future of science men (AU)
Subject(s)
Humans , Ethics , Cloning, OrganismABSTRACT
La biotecnología, aunque tan antigua como la invención del vino y la fermentación de la cerveza por el hombre, tiene en los años 60 del siglo XX, un importante despegue con las técnicas de biología molecular y clonaje de genes foráneos en organismos unicelulares, y el surgimiento de los primeros medicamentos recombinantes. En la década de 1980 y 1990, se obtiene sorprendentes resultados de transgénesis de animales y plantas y ya finalizando el siglo aparece la clonación ó generación de animales idénticos a partir de células somáticas. En este trabajo se valora críticamente las oportunidades y riesgos de la transgénesis y la clonación en el plano ético actual, teniendo en cuenta la amenaza de los seres clónicos, la responsabilidad social de los científicos, la polarización del sistema científico internacional y los códigos morales, además de la ética del profesional científico cubano que responde al principio de que el futuro de nuestra patria tiene que ser necesariamente un futuro de hombres de ciencia.
Even though Biotechnology is as old as the invention of wine and beer fermentation by men, it experiences an important take off in the 60s, with the development of molecular biology techniques and cloning of strange genes in unicellular organisms, and the emergence of the first recombinant medications. In the decade of 1980 and 1990, surprising results in transgenesis of animals and plants are obtained and by the end of the century cloning or generation of identical animals starting from somatic cells is carried out. In this work the opportunities and risks of transgenesis and cloning are analyzed critically taking into account the current ethical perspective, keeping in mind the threat of cloned beings, the social responsibility of scientists, the polarization of the international scientific system and moral codes, as well as the Cuban science professionals ' ethics that responds to the principle that the future of our homeland is necessarily a future of science men.
ABSTRACT
La biotecnología, aunque tan antigua como la invención del vino y la fermentación de la cerveza por el hombre, tiene en los años 60 del siglo XX, un importante despegue con las técnicas de biología molecular y clonaje de genes foráneos en organismos unicelulares, y el surgimiento de los primeros medicamentos recombinantes. En la década de 1980 y 1990, se obtiene sorprendentes resultados de transgénesis de animales y plantas y ya finalizando el siglo aparece la clonación ó generación de animales idénticos a partir de células somáticas. En este trabajo se valora críticamente las oportunidades y riesgos de la transgénesis y la clonación en el plano ético actual, teniendo en cuenta la amenaza de los seres clónicos, la responsabilidad social de los científicos, la polarización del sistema científico internacional y los códigos morales, además de la ética del profesional científico cubano que responde al principio de que el futuro de nuestra patria tiene que ser necesariamente un futuro de hombres de ciencia(AU)
