Abstract
273 Background: B7-H3 is a T cell costimulatory molecule whose expression correlates with increased prostate cancer stage and mortality. We measured serum B7-H3 (sB7-H3) levels in men undergoing sipuleucel-T (sip-T) immunotherapy for castrate-resistant prostate cancer (CRPC) to determine if sip-T modified B7-H3 levels. Methods: We analyzed 41 banked serum specimens before and after sip-T treatment for CRPC. An ELISA test for sB7-H3 was used to measure serum sB7-H3 levels using a standard curve consisting of B7-H3 fusion protein, and a 4 parameter logistic model fit to back-calculate sB7-H3 levels. Each sample was measured in duplicate and the average of these two measurements used. Generalized additive and segmented regression models were used to model the relationship between sB7-H3 level and time to (and from) sip-T treatment. Results: We found that the sB7-H3 assay had a high degree of reproducibility with a Pearson correlation coefficient of 0.9 between the two measurement occasions. Importantly, sB7-H3 had no correlation with prostate specific antigen (PSA) level, indicating that sB7-H3 was providing incremental biological information not contained in the PSA level. Median PSA before sip-T treatment was 6.2 ng/mL [IQR 3.9-14.7] and median PSA post sip-T treatment was 23.4 ng/mL [IQR 9.8-107.4). Median serum sB7-H3 before sip-T treatment was 24.2 ng/dL [IQR 20.3-27.1] and median serum B7-H3 after sip-T treatment was 23.1 ng/mL [IQR 21.8-26.6]. Using a generalized additive model to measure the level of sB7-H3 from time to sip-T treatment, we found a statistically significant relationship between sB7-H3 levels and sip-T treatment, p=0.038. Using segmented linear regression, we found that sB7-H3 levels increased gradually as CRPC worsened prior to sip-T immunotherapy then, at a mean of 24 days after sip-T initiation, sB7-H3 levels started to fall. Conclusions: We found that sB7-H3 levels increased in men with CRPC and that sip-T treatment reversed this trend. Therefore, sip-T may have a positive immunological effect in CRPC irrespective of PSA change. These results suggest that one potential mechanism of action of sipuleucel-T is the reduction of sB7-H3 production by prostate cancer cells.
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