Immunotherapy of advanced prostate cancer: a phase I/II trial using Mycobacterium vaccae (SRL172)

To assess whether a new heat-killed Mycobacterium vaccae preparation (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 stimulate desirable cytokine changes in these patients and modulate the progression of the disease.

Ten patients were given SRL172 intradermally at regular intervals. The serum prostate specific antigen (PSA) level was used as a surrogate marker of response. The proportion of peripheral blood mononuclear cells (PBMC) secreting interleukin 2 (IL2), interferon gamma (IFNgamma) 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.

There were no significant adverse events. In five patients the serum PSA declined during the trial and in two of these there was no concomitant change of therapy apart from vaccination with SRL172. Before vaccination with SRL172 patients had a low proportion of PBMC producing IFNgamma and IL2 (all 10) and a higher proportion secreting IL4 (all three tested), suggesting a predominantly Th2 cytokine profile. After vaccination the proportion of IL4 secreting PBMC fell in all three patients tested. The proportion of IL2 secreting PBMC increased in three patients whose PSA fell. The proportion of IFNgamma-secreting cells remained depressed in nine of 10 patients.

Two patients with advanced hormone-refractory prostate cancer had a PSA response to the vaccination with SRL172. The proportion of PBMC secreting IL2 is a potential marker of response to immunotherapy.