Phase I Study with SV-BR-1 Breast Cancer Cell Line Vaccine and GM- CSF: Clinical Experience in 14 Patients

We evaluated the safety and feasibility of breast cancer vaccine therapy using a new cell line, SV-BR-1, in conjunction with repeated injections of GM-CSF, as a prototype for a subsequent genetically engineered vaccine. Also addressed with this preliminary trial were monitoring effects on quality of life, screening for potential immune responses, and evaluating any clinical effects on tumor progression and patient survival. Fourteen patients with metastatic breast cancer were treated with SV-BR-1 tumor cells. The cell line strongly overexpresses HER2/neu, and has an unusual variety of cytogenetic abnormalities. Irradiated whole-cell suspensions (median dose 14 x 10 6 viable cells) were inoculated via intradermal injection or intralymphatic cannulation, the former usually including an equal amount of irradiated autologous peripheral blood lymphocytes (PBL). Vaccine was initially given at 2-week intervals x3, then monthly. Low-dose cyclophosphamide 300mg/m 2 was given 48-72 hrs prior to vaccine, and GM-CSF (125 mcg) was given subcutaneously immediately prior and for 8 days subsequently. The Kaplan-Meier mean survival for all 14 patients was 17.2 months (CI 5.8-28.5 months) and was 21.1 months (95% CI 5.0-37.2 months) for nine patients treated with the tumor cell/PBL admixture, although there were no clinical regressions. SV-BR-1 as a whole-cell vaccine appears feasible and without obvious major toxicity. The overall survival compares favorably with current Phase I studies. Based on these observations, we have initiated a clinical trial using the SV-BR1 cell line transfected to release GM-CSF in situ with four patients to date. One case responded with clear evidence of tumor regressions in multiple sites and the median survival of 35.0 months is three times longer than usual expectations for salvage programs.