CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer.

Epidermal growth factor receptor (EGFR) is overexpressed in many epithelial tumors and its role in the development of non-small-cell lung cancer (NSCLC) is widely documented. CIMAvax-EGF is a therapeutic cancer vaccine composed by recombinant EGF conjugated to a carrier protein and emulsified in Montanide ISA51. Vaccination induces antibodies against self-EGF that block EGF-EGFR interaction and inhibit EGFR phosphorylation. Five clinical trials were conducted to optimize vaccine formulation and schedule. Then, two randomized studies were completed in advanced NSCLC, where CIMAvax-EGF was administered after chemotherapy, as 'switch maintenance'. The vaccine was very well tolerated and the most frequent adverse events consisted of grade 1/2 injection site reactions, fever, headache, vomiting and chills. CIMAvax was immunogenic and EGF concentration was reduced after vaccination. Subjects receiving a minimum of 4 vaccine doses had a significant survival advantage. NSCLC patients with high EGF concentration at baseline had the largest benefit, comparable with best maintenance therapies.

Inmunosenescencia: efectos de la edad sobre el sistema inmune / Immunosenescence: effects of aging process on immune system

El proceso de envejecimiento provoca cambios en el sistema inmune que afectan su funcionamiento y desarrollo. Estos cambios pueden manifestarse desde la linfopoyesis hasta la respuesta que orquesta el sistema inmune frente a determinada enfermedad o agente infeccioso. Ambas ramas de la inmunidad, innata y adaptativa, se afectan en este proceso, lo que genera un impacto negativo en la respuesta inmune de los ancianos y los predispone a padecer enfermedades infecciosas, cáncer, autoinmunidad y a desarrollar respuestas pobres tras la administración de vacunas(AU)

The aging process produces functional and developmental changes in the immune system. Those changes may appear from lymphopoiesis up to the final response of the immune system facing a certain disease. Both branches of immunity, innate and adaptive, are affected by the aging process; hence these changes can have a negative impact on the immune response of elderly patients and increase their susceptibility to infectious diseases, cancer and decreased vaccine efficacy(AU)

Inmunosenescencia: efectos de la edad sobre el sistema inmune / Immunosenescence: effects of aging process on immune system

El proceso de envejecimiento provoca cambios en el sistema inmune que afectan su funcionamiento y desarrollo. Estos cambios pueden manifestarse desde la linfopoyesis hasta la respuesta que orquesta el sistema inmune frente a determinada enfermedad o agente infeccioso. Ambas ramas de la inmunidad, innata y adaptativa, se afectan en este proceso, lo que genera un impacto negativo en la respuesta inmune de los ancianos y los predispone a padecer enfermedades infecciosas, cáncer, autoinmunidad y a desarrollar respuestas pobres tras la administración de vacunas...

The aging process produces functional and developmental changes in the immune system. Those changes may appear from lymphopoiesis up to the final response of the immune system facing a certain disease. Both branches of immunity, innate and adaptive, are affected by the aging process; hence these changes can have a negative impact on the immune response of elderly patients and increase their susceptibility to infectious diseases, cancer and decreased vaccine efficacy...

Immunosenescence and gender: a study in healthy Cubans.

BACKGROUND: The progressive decline in the immune function during ageing is termed immunosenescence. Previous studies have reported differences between males and females in the distribution and cell responses of lymphocyte subsets. Most studies of immunosenescence have been done in populations of industrialized countries living in a rather cold environment, and facing lower antigenic challenges such as Cytomegalovirus (CMV). The aim of this study was to determine the effect of ageing on lymphocytes in a population with a high prevalence of CMV infection in all ages, and to compare gender differences related to the immunosenescence markers. RESULTS: Different populations of peripheral blood leukocytes from healthy young and old IgG-CMV seropositive individuals were examined using flow cytometry. With age, the number and frequency of B cells and T cells significantly decreased, while highly differentiated T cells increased. Such changes were different in males and females. The age-associated decline of less differentiated lymphocyte subsets (CD19, CD4 and CD8 cells) and the increase of highly differentiated T cells were more prominent in females. In males, there were no significant changes in CD19, CD4 and CD8 subsets but there was a significant increase in the proportion of highly differentiated T cells. CONCLUSION: Shifts in lymphocyte subsets distribution were influenced by age and gender in an IgG-CMV seropositive population. These results suggest different patterns of immunosenescence in respect to gender differences. These patterns could have implications in the design of immunotherapy in the elderly.

Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer.

PURPOSE: We show the result of a randomized phase II clinical trial with an epidermal growth factor (EGF)-based cancer vaccine in advanced non-small-cell lung cancer (NSCLC) patients, evaluating immunogenicity, safety, and effect on survival. PATIENTS AND METHODS: Eighty patients with stage IIIB/IV NSCLC after finishing first-line chemotherapy were randomly assigned to receive best supportive care or EGF vaccinations. RESULTS: Vaccination was safe. Adverse events were observed in less than 25% of cases and were grade 1 or 2 according to National Cancer Institute Common Toxicity Criteria. Good anti-EGF antibody response (GAR) was obtained in 51.3% of vaccinated patients and in none of the control group. Serum EGF concentration showed a major decrease in 64.3% of vaccinated patients. GAR patients survived significantly more than those with poor antibody response (PAR). Also, patients whose serum EGF dropped below 168 pg/mL survived significantly more than the rest. There was a trend to an increased survival for vaccinated patients compared with controls. The survival advantage for vaccinated patients compared with controls was statistically significant in the subgroup of patients with age younger than 60 years. CONCLUSION: Vaccination with EGF was safe and provoked an increase in anti-EGF antibody titers and a decrease in serum EGF. There was a direct correlation between antibody response and survival. There was a direct correlation between decrease in serum EGF and survival. In patients younger than 60 years, vaccination was associated with increased survival.

Treatment of NSCLC Patients with an EGF-Based Cancer Vaccine

Epidermal Growth Factor (EGF) promotes tumor cell proliferation and survival uponbinding to its receptor. We have developed a new active specific immunotherapy based on EGF deprivation. In the present paper, we show the results of a Phase I trial in 43patients with advanced non-small cell lung cancer (NSCLC) who received the EGF vaccine. Patients who had already received first line therapy were randomized to receive a singleor double dose of the EGF vaccine, weekly for four weeks and monthly thereafter. No significant toxicity was seen after vaccination. Adverse events consisted primarily of fever,chills, nausea, vomiting and flushing. Fifteen patients (39percent) developed a good antibody response (GAR) against EGF. The geometric mean of the antibody titer was higher in thedouble dose group. EGF concentration was quantified in serum. An inverse correlation between anti-EGF antibody titers and EGF concentration was seen after immunization. Vaccinated patients achieved median survival times of 8.23 months from randomization. Patients who received the double dose of treatment showed a trend toward increased survival in comparison with patients who received the single dose. GAR and patients in whom the serum EGF decreased below the 168 pg/ml cut-off point had a significantly better survival when compared to poor responders or patients in which the EGF levels were not considerably reduced. Our results confirm the immunogenicity of the EGF vaccine in the treatment of patients with advanced stage NSCLC. Antibody titers and serum EGF levels appear to correlate with patient survival(AU)

Factor de Crecimiento Epidérmico (FEAG) promueve la proliferación celular tumoral y la supervivencia a unión a su receptor. Hemos desarrollado un nuevo principio activo basado en la inmunoterapia específica sobre la privación FEAG. En el presente trabajo, mostramos los resultados de un ensayo fase I en 43 pacientes con avanzado de células no pequeñas de cáncer de pulmón (CPNM) que recibieron la vacuna contra el FEAG. Los pacientes que ya habían recibido terapia de primera línea fueron asignados aleatoriamente a recibir un solo o doble dosis de la vacuna contra el FEAG, la semana durante cuatro semanas y mes. No toxicidad significativa fue visto después de la vacunación. Los eventos adversos se componía fundamentalmente de fiebre, escalofríos, náuseas, vómitos y enrojecimiento. Quince pacientes (39 por ciento) desarrollaron un buen anticuerpo respuesta (GAR) contra FEAG. La media geométrica de los anticuerpos fue mayor en el dosis doble grupo. FEAG se cuantificó la concentración en el suero. Una correlación inversa entre la lucha contra la FEAG los títulos de anticuerpos y FEAG concentración fue visto después de la vacunación. Pacientes vacunados alcanzado los tiempos medios de supervivencia de 8,23 meses desde la aleatorización. Los pacientes que recibieron la dosis doble de tratamiento mostraron una tendencia hacia un mayor la supervivencia en comparación con los pacientes que recibieron la dosis única. GAR y los pacientes en los cuales el suero FEAG disminuyó por debajo de los 168 pg / ml punto de corte tenía una significativa una mejor supervivencia en comparación con los pobres o los pacientes con respuesta en la que el FEAG niveles no se redujo considerablemente. Nuestros resultados confirman la inmunogenicidad de la vacuna contra el FEAG en el tratamiento de pacientes con CPNM avanzado. Los títulos de anticuerpos en suero y FEAG niveles parecen correlacionarse con la supervivencia de los pacientes

Estabilidad acelerada de tabletas de levodopa-carbidopa (250-25 mg) / Accelerated stability of levodopa-carbidopa tablets (250-25 mg)

Se realizó el estudio de estabilidad acelerada de tabletas de levodopa-carbidopa (250-25 mg) con el empleo de un método de cromatografía líquida de alta resolución y se comprobó su especificidad para estos fines. Se analizó la influencia de medios degradantes artificiales sobre los productos activos, además del efecto de la humedad sobre la estabilidad del producto, colocándolo en hidrostatos con humedades controladas. Este medicamento, producción nacional, cumplió con las especificaciones de calidad descritas en la USP 23 y mostró una alta estabilidad térmica

Estabilidad acelerada de tabletas de levodopa-carbidopa (250-25 mg) / Quick stability of levodopa-carbidopa pills (250-25 mg)

Se realizó el estudio de estabilidad acelerada de tabletas de levodopa-carbidopa (250-25 mg) con el empleo de un método de cromatografía líquida de alta resolución y se comprobó su especificidad para estos fines. Se analizó la influencia de medios degradantes artificiales sobre los productos activos, además del efecto de la humedad sobre la estabilidad del producto, colocándolo en hidrostatos con humedades controladas. Este medicamento, producción nacional, cumplió con las especificaciones de calidad descritas en la USP 23 y mostró una alta estabilidad térmica(AU)