ASCO GU 2020: The Association of Humoral Antigen Spread with Cytotoxic T Lymphocyte Activity after Sipuleucel-T Treatment in Two Phase II Clinical Studies: STAMP and STRIDE

San Francisco, California ( Cytotoxic T lymphocyte activity (CTL) targeting the primary antigens PA2024 (human prostatic acid phosphatase [PAP] fused to human granulocyte macrophage colony stimulating factor), the immunogen used to manufacture Sipleucel-T (SIP-T), and PAP following treatment with SIP-T in men with hormone sensitive and castrate resistant prostate cancer, is associated with improved overall survival.

Additionally, increased antibody responses to non targeted secondary antigens were associated with improved overall survival in the IMPACT clinical trial.

In this study, the authors evaluated the hypothesis that the downstream impact of targeting the primary antigens is the destruction of target sales. This cell killing results in the release of antigens that generate a secondary antibody response, extending the effect through a humoral response to have synergistic effects on overall survival.

The objective was to evaluate the correlation between CTL activity expression and spread measures in the STAMP (NCT01487863) (a phase II trial, evaluating sipuleucel-T and concurrent vs, sequential abiraterone acetate + prednisone in metastatic castration-resistant prostate cancer patients), and STRIDE (NCT01981122) (A study comparing concurrent vs sequential enzalutamide with sipuleucel-T in patients with metastatic castration-resistant prostate cancer) clinical trials.

Table 1 demonstrates the number of patients included per trial. Figure 1 demonstrates the PA2024 and PAP-specific normalized CTL activity, while figure 2 shows the antigen spread beyond primary antigens.

table 1 numbers included per trial

figure 1 normalized ctl activity

figure 2 antigen spread beyond primary antigens

The authors stated in their poster that PA2024-specific CTL activity at week 26 is positively correlated at multiple time points with antibody responses to the following:

  • 2 primary antigens (PA2024 and PAP)
  • 4 secondary antigens (PSA, KRAS, ERAS, AND KLK2)

CTL activity at week 26 was also positively correlated with the numbers of secondary antibody response of weeks 10 and 14 as shown in figure 3a,3b and 3c. The secondary antibody responses at week 10 are correlated to the release of additional antigens following the observed start of CTL activity.

It was also shown that the numbers of secondary antibody responses at weeks 10 and 14 were positively correlated with overall survival.

Figure 3a, 3b, 3c:

figure 3 correlation between ctl activity and antigen spread

In conclusion, treatment with SIP-T in metastatic castrate resistant prostate cancer patients appears to invoke the tumor immunity cycle, wherein tumor cell death releases antigens that act as secondary epitopes resulting in humoral antigen spread.

Presented by: Daniel Petrylak, Professor of Medicine (Medical Oncology) and of Urology; Co-Leader, Cancer Signaling Networks, Yale Cancer Center, New Haven, CT

Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA @GoldbergHanan at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California