IMMUNOTHERAPY OF ADVANCED PROSTATE-CANCER - A PHASE-I PHASE-II TRIAL USING MYCOBACTERIUM-VACCAE (SRL172)

Objective To assess whether a new heat-killed Mycobacterium vaccae pre paration (SRL172), which enhances cell-mediated immunity and has been proposed for use as an immunotherapeutic agent against cancer, is safe in patients with advanced hormone-refractory prostate cancer, can sti mulate desirable cytokine changes in these patients and modulate the p rogression of the disease. Patients and methods Ten patients were give n SRL172 intradermally at regular intervals. The serum prostate specif ic antigen (PSA) level was used as a surrogate marker of response. The proportion of peripheral blood mononuclear cells (PBMC) secreting int erleukin 2 (IL2), interferon gamma (IFN gamma) and interleukin 4 (IL4) was measured by flow cytometry (FACS) before and after vaccination to assess whether the treatment induced a Th2 (predominantly humoral) to Th1 (predominantly cell-mediated) switch. Results There were no signi ficant adverse events. In five patients the serum PSA declined during the trial and in two of these there was no concomitant change of thera py apart from vaccination with SRL172. Before vaccination with SRL172 patients had a low proportion of PBMC producing IFN gamma and IL2 (all 10) and a higher proportion secreting IL4 tall three tested), suggest ing a predominantly Th2 cytokine profile. After vaccination the propor tion of IL4 secreting PBMC fell in all three patients tested. The prop ortion of IL2 secreting PBMC increased in three patients whose PSA fel l. The proportion of IFN gamma-secreting cells remained depressed in n ine of 10 patients, Conclusion Two patients with advanced hormone-refr actory prostate cancer had a PSA response to the vaccination with SRL1 72. The proportion of PBMC secreting IL2 is a potential marker of resp onse to immunotherapy.