A feasibility and safety study of vaccination with Poly-ICLC and peptide-pulsed dendritic cells in patients with advanced pancreatic adenocarcinoma.

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Journal: J Clin Oncol 34, 2016 (suppl; abstr e14579)
Published: 2016-06-03

Authors:
Shikhar Mehrotra, Carolyn D. Britten, Steve Hsukwo Chin, Mohamed L. Salem, Colleen Cloud, Michelle H. Nelson, Chrystal Paulos, Elizabeth Garrett-Mayer, Mark P. Rubinstein, Zihai Li, David J. Cole; Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; Department of Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; Eli Lilly and Company, Carmel, IN; Tanta University, Tanta, Egypt; Department of Microbiology & Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; Departments of Surgery and Microbiology & Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC; Medical University of South Carolina, Charleston, SC; Medcl Univ of South Carolina, Charleston, SC; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC

ABSTRACT

Background: Dendritic cells (DCs) shape the quantity and quality of anti-tumor immunity in patients with cancer. We hypothesized that DC-based immunotherapy, in conjunction with a novel long-lasting TLR3 agonist, Poly-ICLC, is a promising approach against metastatic or locally advanced unrespectable pancreatic cancer (PC).

Methods: To address our clinical concept, we generated autologous DCs from peripheral blood monocytes from HLA-A2+ patients with pancreatic cancer (PC) and pulsed DCs with three immunogenic A2-restricted epitopes: human telomerase reverse transcriptase (hTERT, TERT572Y), carcinoembryonic antigen (CEA; Cap1-6D) and survivin (SRV.A2). Patients received four intradermal injections of 1 x 107peptide-pulsed DC vaccines every 2 weeks (Day 0, 14, 28 and 42). Concurrently, patients received intramuscular administration of Poly-ICLC at 30 µg/Kg on vaccination days (Day 0, 14, 28, and 42), as well as on Days 3, 17, 21, 31, 37 and 45). Our primary objective was to assess safety and feasibility. The effect of DC vaccination on immune response was measured at each DC injection time point by enumerating the phenotype and function of patient T cells.

Results: A total of 12 patients underwent leukapheresis: 9 patients with metastatic disease, and 3 with locally advanced unresectable PC. Manufacturing of vaccines was uniformly successful. Study treatment was well tolerated, with the most common symptoms being fatigue and/or self-limiting flu-like symptoms. Among the 8 patients who underwent imaging on Day 56, 4 had stable disease and 4 had disease progression. Overall, the median survival was 7.7 months from date of leukapheresis. One patient has survived for 28 months. IFN-gamma ELISPOT and MHC class I – tetramer analysis, before and after vaccination, revealed effective generation of antigen-specific T cells in 3 patients with stable disease.

Conclusions: Vaccination with Poly-ICLC and peptide-pulsed dendritic cells is safe and induces a measurable tumor specific T cell population in patients with advanced PC. Clinical trial information: NCT01410968

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