Results of a study conducted to further elucidate the mechanism of action of sipuleucel-T (Provenge) as treatment for advanced prostate cancer provide fairly convincing demonstration that the autologous cellular immunotherapy agent induces T-cell responses in humans, said Charles G. Drake, MD, PhD.
The research, presented at the American Society of Clinical Oncology annual meeting in Chicago, evaluated the proliferative and lytic phenotypes of antigen-specific T helper (Th) cells and cytotoxic T lymphocytes (CTLs) in patients treated with sipuleucel-T in clinical trials. In addition, it investigated the correlation between CTL activity and overall survival in the treated patients.
Also see: A promising target for immunotherapy?
Assays showed that sipuleucel-T generated robust proliferation of the immune cells, particularly of the CTLs, and that as early as 6 weeks post-treatment and persisting for at least 26 weeks, the CTLs were capable of cytolytic activity. Furthermore, an association was found between the magnitude of the antigen-specific CTL response persisting at week 26 and overall survival.
“The assays used in this study, which are based on quantifying T-cell proliferation and production of effector cytokines, are more sensitive than previously used techniques, and therefore allow us to detect patients who seem to respond immunologically to the treatment,” explained Dr. Drake, of Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York.
“The correlation identified between increased magnitude of the CTL responses and longer survival suggests that patients who develop a T-cell response to sipuleucel-T may be more likely to benefit clinically. However, because this is a retrospective study, we cannot separate correlation from causation. Therefore, we cannot determine whether improved T-cell response actually drove survival or if healthy patients destined for longer survival were more likely to mount a better T-cell response when treated with sipuleucel-T.”