Sipuleucel-T Induces PAP-Specific CTL Activity in mCRPC Patients

Chicago—Sipuleucel-T (sip-T) is an autologous cellular immunotherapy approved in the United States for patients with asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Sip-T is produced by culturing peripheral blood mononuclear cells with the immunogen PA2024 (prostatic acid phosphatase [PAP] conjugated to granulocyte macrophage colony-stimulating factor).

A biomarker that can identify patients with mCRPC who are likely to respond well to sip-T may be useful in making treatment decisions in that patient population. There is a correlation between PA2024 and PAP cellular and humoral immune responses induced by sip-T and prolonged overall survival. Further, robust cytolytic T lymphocyte (CTL) activity post sip-T treatment has been reported.

Using CD107a expression, a cell surface surrogate marker, Charles G. Drake, MD, and colleagues conducted a study to examine the relationship between sip-T lytic activity and overall survival in patients with mCRPC. They reported results during a poster session at the ASCO 2018 Annual Meeting in a poster titled Relationship between Sipuleucel-T (sip-T) Cytolytic T Lymphocyte (CTL) and overall survival (OS) in patients (pts) with Metastatic Castration-Resistant Prostate Cancer (mCRPC).

Flow cytometry was used to identify PA2024- and PAP-specific CD+8 T (CTL) cells expressing CD107a at baseline (prior to sip-T infusion) and at 6 and 26 weeks post-sip-T infusion in patients who were treated in the STRIDE (n=12) and STAMP (n=10) trials and in three healthy volunteers.

At weeks 6 and 26 after sip-T treatment, CTL activity was significantly (P<.0001) increased from baseline in response to PA2024 and PAP. At week 36, a strong correlation between PAP and PA2024-specific CTL activity was seen (Pearson’s R=0.8973; P<.0001); there was not a strong correlation at week 6 or at baseline.

At week 26, there were positive correlations between both PAP-specific CTL activity (R=0.5187; P=.0134) and PA2024-specific activity (R=0.6735; P=.0006) and overall survival. At 26 weeks, median overall survival for patients with PAP-specific CD107a expression above or below the median CTL activity was 37.1. Also at 26 weeks, median overall survival for patients with PA2024-specific CD107a expression above or below the median CTL activity was 25.2 months.

In summary, the researchers said, “These analyses demonstrate that sip-T induced a robust PAP-specific CYL activity, indicative of tumor lytic activity, which is positively correlated with prolonged overall survival in mCRPC patients. This finding is a significant addition to the elucidation of the mechanism of sip-T induced immune responses and overall survival benefit.”

Clinical trial information: STRIDE: NCT01981122; STAMP: NCT01487863

Source: Drake CG, Antonarakis ES, Petrylak DP, et al. Relationship between sipuleucel-T (sip-T) cytolytic T lymphocyte (CTL0 activity and overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Abstract of a poster presented at the American Society of Clinical Oncology 2018 Annual Meeting, June 2, 2018, Chicago, Illinois.