Increased lymphopenia results in higher percentages of FoxP3+ T cells in patients reconstituted by PBMC adoptive transfer and vaccinated (41.36)

• Published in: The Journal of immunology (1950) 2009-04, Vol.182 (1_Supplement), p.41-41.36
• Main Authors: Thompson, James A, Assmann, Ilka, Haley, Daniel, Moudgil, Tarsem L., Jensen, Shawn M., Poehlein, Christian H., Hu, Hong-Ming, Walker, Edwin B., Sacks, Natalie, Hege, Kristen, Curti, Brendan, Urba, Walter J., Fox, Bernard A.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.182.Supp.41.36

In clinical trials therapeutic tumor vaccines have failed to provide evidence of efficacy. Based on preclinical tumor models showing that vaccination during homeostasis-driven proliferation improved therapeutic efficacy, we performed a translational phase I/II clinical trial in men with metastatic hormone-refractory adenocarcinoma of the prostate. This strategy has the theoretical advantage that it eliminates regulatory T cells (Treg). Patients were randomized to cohort A, B or C. Cohort A patients (n = 5) received prostate GVAX TM (two prostate cancer cell lines that secrete GM-CSF, Cell Genesys Inc.) vaccination only. Cohort B (n = 5) received cyclophosphamide followed by reinfusion of autologous PBMC and vaccine (GVAX). Cohort C patients (n=5) received same treatment as Cohort B with the addition of fludarabine. We hypothesized that the most lymphopenic patients would have the fewest Treg. While all cohorts showed an increase in the total number and frequency of peripheral Treg, the most lymphopenic patients (cohort C) had the greatest fold increase in peripheral Treg at weeks 2-6 (2.3,1.2,0.7 / p