EXTH-22. TARGETING A NEWLY DISCOVERED IMMUNE CHECKPOINT, SIGLEC-15, INCREASES ONCOLYTIC EFFICACY OF ZIKA VIRUS (ZIKV) IN GLIOBLASTOMA (GBM)

Abstract We are developing ZIKV as a therapy for GBM. previously demonstrated specifically kills GBM stem cells. Using GL261 and CT2A mouse models, induces CD8+ T-cell mediated anti-tumor response leads to 65% 40% long term survivors, respectively (0%-untreated controls). treatment significantly increases the number of myeloid cells in tumor microenvironment (with about 10,000 infiltrating macrophages per ZIKV-treated brain, 1,000 untreated brain). hypothesized that by targeting immune checkpoint, we would further enhance efficacy. Siglec-15 is newly described anti-siglec-15 antibody currently clinical trial patients with advanced or metastatic solid tumors (NCT03665285). While there was no effect alone, observed increased efficacy when combined (cure rate: GL261-70%, CT2A-60% ZIKV+anti-siglec-15 antibody; GL261-20%, CT2A-0% alone; GL261-30%, CT2A-25% GL261-0%, without treatment). Since recurrence major problem, performed re-challenge experiments cured mice at 6 months. Mice treated had 70% long-term survival, compared 30% age matched controls. This supports our earlier findings an immunological after engenders long-term, tumor-specific, surveillance. Lastly, used knockout confirm observations. After treating bearing ZIKV, animals were cured. There significant difference survival between CT2A-bearing wild type hosts. Taken together, work suggests putative suppressor cells, oncolytic its ensuing anti-cancer cell activated effects, may be effective tool neuro-oncology. Targeting also other cytotoxic therapies.