Breast cancer: Draining lymph node of vaccination site targeted by adjuvant GM-CSF in an autologous vaccine

Abstract

13506 Background: We have reported the sensitization against Tumor Associated Antigens (TAA) and the tumor antiprogressive effect of Autologous Thermostable Hemoderivative-Cancer Vaccine (ATH-CV) in breast cancer patients (E. Garcia-Giralt et al ASCO, 2006). Systemic immune response elicited by TAA is started by a locoregional immune response at the microenvironment constituted by the antigens source and the draining lymph node. The antigens source can be a tumor or a vaccination site and respectively, the draining lymph node is the sentinel lymph node (SLN) or the Sentinel Immunized Node (SIN). Tolerogenic or protective locoregional immune response is decisional because it starts a corresponding systemic immune response, tolerogenic or protective. GM-CSF is a conditioner of SLN and SIN, switching the locoregional immune responses from tolerogenic to protective (ML Disis et al Blood, 1996; AJ Cochran et al Nat Rev Immunology, 2006). Therefore, to optimize the ATH-CV antitumoral effect, we have explored GM-CSF as a locoregional adjuvant. Methods: Thirty six M1 breast cancer patients, ER+,HER 2-, hormone and chemotherapy resistant, performance status = 2, and CA 15–3 rising level, were included in this prospective, IRB-approved phase I/II trial. Patients were 3-group (G) randomized (12 each), submitted to different treatments: G1, no additional oncology treatment; G2, ATH-CV; G3, ATH-CV plus GM-CSF at vaccination site 150 μg/day, 5 days. Statistic assessment (Student’s t-test) was performed at the 30-day end point: ATH sensitization by Delayed Type Hypersensibility test (DTH) and Lymphocyte Proliferative Assay (LPA); PSA serum level and immunophenotyping of lymph node cells in biopsies of SIN scintigraphy-localized. Results: Significant differences (p<0.05): DTH test > 5 mm: G1, 0/12; G2, 3/12 and G3, 6/12. LPA > 2.0: G1, 0/12; G2, 4/12 and G3, 7/12. Immunophenotyping: MHC-II+CD83+ (Mature Dendritic Cells):G3>G2>G1. 30 days CA 15–3 increase: G1>G2>G3. No relevant toxicities were evidenced. Conclusions: In advanced breast cancer, ATH-CV sensitization and tumor antiprogressive effect were potentiated by GM-CSF as local adjuvant. Increase of SIN mature dendritic cells is suggested as mechanism of action. No significant financial relationships to disclose.