EXTH-94. LOCALIZED INTRATUMORAL TREATMENT WITH ADOPTIVE T CELL THERAPY FOLLOWED BY ONCOLYTIC ADENOVIRUS DELTA-24-RGDOX INDUCES SUSTAINABLE REGRESSION OF DISSEMINATED SOLID TUMORS THROUGH ANTIGEN SPREAD

Abstract Tumor-targeting biological therapies, including adoptive T cell therapy (ACT) and oncolytic viruses, are being tested clinically to address the challenges in treating advanced solid tumors with heterogeneity immune suppressive microenvironment (TME). Since complementary properties of these two approaches have been observed, we hypothesize that localized intratumoral treatment combination ACT Delta-24-RGDOX (third generation adenovirus developed by our group) induces not only potent therapeutic effect treated tumor but also abscopal benefit eliminate distant disseminated tumors. Using a B16-C57BL/6 melanoma model C57BL/6 mice, found gp100-specific CD8+ cells injected into first subcutaneous (s.c.) showed tropism for s.c. intracranial tumors, draining lymph nodes, compared spleen, blood normal brain hemisphere. In B16-OVA-C57BL/6 s.c./s.c. model, injections following increased total cytotoxic presence within both gp100- OVA- specific cells. Further analysis revealed reduced exhaustion OVA-specific while kept at low level. Moreover, augmented activity splenocytes against other tumor-associated antigens (OVA, TRP2) than gp100. Consequentially, was more inhibit untreated growth caused improved survival rate either agent alone (p < 0.05). Importantly, observed relapse regressed group, group. The survivors memory rechallenging B16-OVA Collectively, data demonstrate followed global activation antigen spread expand antitumor repertoire, leading efficacious systemic anti-tumor immunity sustainable regression.