RESUMEN
Immunotherapy, using peptide-based cancer vaccines is being studied to assess its potential in breast cancer. Trials of HLA-restricted peptide vaccines have been difficult to enroll given HLA subtype restrictions. It is necessary to determine the prognostic significance of HLA-status in breast cancer if patients who are ineligible to receive a vaccine due to their HLA-status are used as controls. The impact of targeted tumor associated antigen expression, when it effects eligibility is also important. We examined control patients from two randomized phase II trials that tested HER2-peptide vaccines to determine the effect of HLA-A2 status and HER2 expression on disease-free survival. The analysis showed that HLA-A2-status does not affect disease-free survival, regardless of HER2 expression suggesting that HLA-A2 negative patients can be used as control patients. Additionally, HER2 over-expression was associated with a better disease-free survival in this population, underscoring the need for additional therapies in HER2 low-expressing breast cancer. ClinicalTrials.gov Identifier: NCT00524277.
Asunto(s)
Neoplasias de la Mama/inmunología , Vacunas contra el Cáncer/inmunología , Antígeno HLA-A2/genética , Inmunoterapia/métodos , Receptor ErbB-2/genética , Adulto , Anciano , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/mortalidad , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Humanos , Persona de Mediana Edad , Mutación/genética , Recurrencia Local de Neoplasia , Receptor ErbB-2/inmunología , Proyectos de Investigación , Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Vacunación , Vacunas de SubunidadRESUMEN
Nelipepimut-S (formerly known as E75) is an immunogenic peptide from the HER2 protein that is highly expressed in breast cancer. The NeuVax™ (Galena, OR, USA) vaccine, nelipepimut-S plus granulocyte-macrophage colony-stimulating factor, is designed for the prevention of clinical recurrences in high risk, disease-free breast cancer patients. Although cancer vaccines such as NeuVax represent promising approaches to cancer immunotherapy, much remains to be elucidated regarding their mechanisms of action: particularly given that multiple cancer vaccine trials have failed to demonstrate a correlation between immunologic data and clinical outcome. Here, we briefly discuss our clinical trial experience with NeuVax focusing on immunologic response data and its implication on how the immune system may be affected by this peptide vaccine. Most importantly, we demonstrate the potential capability of certain immunologic assays to predict clinical benefit in our trials.