Background: Sip-T, an FDA-approved autologous immunotherapy for pts with asymptomatic or minimally symptomatic metastatic castration-resistant PC (mCRPC), is manufactured from peripheral blood mononuclear cells cultured with PA2024, a fusion antigen of prostatic acid phosphatase (PAP) conjugated to granulocyte macrophage colony-stimulating factor. In sip-T–treated pts, antibody responses to PA2024/PAP (target antigens) and AgS (antibody responses to secondary [2°] antigens) correlate with improved OS (Sheikh 2013; GuhaThakurta 2015). We assessed if a greater magnitude of AgS would be observed in an earlier PC disease stage when the immune system is more intact. Methods: Pt serum was from 1 non-metastatic, androgen-dependent PC (ADPC) sip-T trial (STAND, sip-T + androgen deprivation, NCT01431391) and 3 mCRPC sip-T trials (IMPACT, sip-T vs control, NCT00065442; STAMP, sip-T + abiraterone acetate, NCT01487863; STRIDE, sip-T + enzalutamide, NCT01981122). Using a Luminex assay, mean fold-change in IgG responses to target and 2° cancer-related antigens (PSA, LGALS3, LGALS8, ERAS, KRAS, KLK2) was evaluated from baseline to wk 6. Results: AgS was evaluated in 308 pts. The mean fold-change in IgG responses to target antigens was greater for ADPC vs mCRPC pts (p < 0.01). Moreover, the magnitude of IgG responses was greater for most 2° antigens in ADPC vs mCRPC pts (p < 0.05; Table), except for PSA and KLK2 in ADPC vs STRIDE pts. Conclusions: The magnitude ofantibody responses to target and 2° antigens was greater earlier in the PC disease course, consistent with increased antigen-presenting cell activation in ADPC vs mCRPC pts. Increased AgS likely reflects stronger sip-T–induced immune responses, previously associated with extended OS in mCRPC (Sheikh 2013; GuhaThakurta 2015). Future research is warranted on the clinical benefit of sip-T earlier in the PC disease course and the potential impact of androgen suppression on the magnitude of AgS and outcomes. Clinical trial information: NCT01431391; NCT00065442; NCT01487863; NCT01981122

^•p < 0.01, ^◊p < 0.05 mean fold-change greater in STAND. ns = not significant.