T Lymphocyte Activation and Proliferation with BCG Stimulation of Patients Receiving Dendritic Cell Immunotherapy: A Phase II DCVax-Direct Trial Jeffrey Lin, Joseph Antonios, Sylvia Odesa, Horacio Soto, Robert M Prins, Linda M Liau 695 Charles E. Young Drive South Gonda 1554 Los Angeles, CA 90095
DCVax-Direct is an autologous cellular immunotherapy involving intratumoral injection to solid tumors as an adjuvant traditional therapies. The injection consists of autlogous DCs activated with bacillus Calmette Guerin (BCG) and interferon (IFN)-gamma. Culture with BCG and IFN-gamma activates DCs, upregulating cell surface proteins involved in antigen presentation and T cell stimulation. Patient peripheral blood monocytes (PBMC) and serum were collected at day 0, week 8, and week 16 before each vaccination. We hypothesize that the vaccine creates an inflammatory response, and exposure of PBMCs to BCG will cause T cell activation and proliferation. Luminex technology was used to evaluate cytokine levels in patient serum. PBMCs were labeled with Cell Proliferation Dye (CPD) and cultured with inactivated BCG, and T cell proliferation was assessed using fluorescent target array technology. Levels of proinflammatory cytokines were higher and anti-inflammatory cytokines were lower in serum collected at later time points. CD4+ and CD8+ T cells exposed to BCG showed increased proliferation in patient PBMCs collected at later time points. The data suggest that treatment with DCVax Direct promotes an inflammatory response that can decrease tumor burden through upregulation of proinflammatory cytokines. Activation and proliferation of lymphocytes exposed to BCG suggest that DCs are presenting BCG and likely tumor antigens to patient T cells allowing for a targeted immune response.
Submitted by jelin@mednet.ucla.edu, under the supervision of Linda, Liau M.D. Ph.D., submited on July 24, 2014
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