A phase I study of recombinant (r) vaccinia-CEA(6D)-TRICOM and rFowlpox-CEA(6D)-TRICOM vaccines with GM-CSF and IFN-α-2b in patients with CEA-expressing carcinomas.

摘要: Prime-boost vaccination with recombinant (r) vaccinia(V)-CEA(6D)-TRICOM (triad of co-stimulatory molecules B7.1, ICAM-1 and LFA-3) rFowlpox(F)-CEA(6D)-TRICOM infect antigen-presenting cells direct expression molecules. We hypothesized that co-administration vaccine GM-CSF interferon alpha (IFN-α) would have efficacy in CEA-expressing cancers. Patients cancers received the rV-CEA(6D)-TRICOM subcutaneously (s.c.) on day 1 followed by s.c. to injection site days 1–4. In Cycle 1, patients thrice weekly injections IFN-α-2b week after rV-CEA(6D)-TRICOM. Cycles 2–4, same rF-CEA(6D)-TRICOM was given. The first cohort no IFN dose escalation IFN-α subsequent cohorts. Thirty-three were accrued (mean 59.8 years). Grade 3 toxicities included fatigue hyperglycemia. 4–5 adverse events (unrelated treatment) confusion (1), elevated aspartate transaminase (AST)/alanine (ALT) sudden death (1). No had a partial response, eight exhibited stable disease ≥3 months. Median progression-free survival overall (OS) 1.8 6.3 months, respectively. Significantly higher serum CD27 levels observed therapy (p = 0.006 post 1–2 cycles, p = 0.003 p = 0.03 4–7 cycles) 42 % assayed developed CEA-specific T cell responses. Pre-treatment myeloid-derived suppressor correlated (p = 0.04). Administration led significantly increased OS (p = 0.02) compared alone. While regimen produced clinical responses, administration associated improved survival.