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Background: Sip-T is an FDA-approved immunotherapy for patients pts ith asymptomatic or minimally symptomatic metastatic CRPC. Sip-T is manufactured from autologous peripheral blood mononuclear cells cultured ith the immunogen PA2024, a fusion antigen of prostatic acid phosphatase PAP conjugated to granulocyte macrophage colony-stimulating factor GM-CSF . In sip-Ttreated pts, antibody and T cell responses to PA2024 andor PAP correlate ith improved overall survival. To further elucidate the mechanism of sip-Tinduced immune responses, e evaluated the proliferative and lytic ability of PA2024- and PAP-specific CD8+ T cells. Methods: Mononuclear blood cells ere labeled ith the membrane dye carboxyfluorescein succinimidyl ester CFSE and cultured ith PA2024 or PAP. In vitroproliferative and lytic CD8+ cytotoxic T lymphocyte [CTL] T cell responses to these antigens ere evaluated by flo cytometry. For proliferation, progressive dilution of CFSE as measured; for CTL activity, the loss of intracellular granzyme B GzB as assessed. Pt samples ere obtained from 2 sip-T clinical trials STAND NCT01431391 and STRIDE NCT01981122 , hormone-sensitive and CRPC pts, respectively. Results: Six k after sip-T administration, CD8+ PAP- and PA2024-specific responses ere observed n = 14 pts assessed . The magnitude of PA2024-specific CD8+ proliferative responses as greater than that for PAP-specific responses. CD8+ T cells from a subset of pts ho exhibited PA2024- andor PAP-specific proliferative responses ere assessed for lytic ability. After in vitro antigen stimulation, intracellular GzB as significantly decreased compared ith a no-antigen control p lt 0.05 , in all samples evaluated PA2024 n = 14 and PAP n = 13 , demonstrating CTL activity. Conclusions: Sip-T induced CD8+ CTL proliferation against the target antigens PAP and PA2024. Moreover, antigen-specific CTL activity provides the first direct evidence that sip-T can induce tumor cell lysis. These antigen-specific CD8+ lytic abilities ere observed ithin 6 k, suggesting rapidly generated immune responses folloing sip-T. Clinical trial information: lta href=http:clinicaltrials.govshoNCT01431391 and NCT01981122 NCT01431391 and NCT01981122,J Clin Oncol 34, 2016 suppl; abstr e23116 ,NCT01431391 and NCT01981122Publication Only Tumor Biology