EXTH-98. ENHANCING T CELL TRAFFICKING OF CD3-ENGAGING IMMUNOTHERAPY TO TUMORS OF THE CENTRAL NERVOUS SYSTEM

Abstract BACKGROUND Effective immunotherapy against tumors of the central nervous system (CNS) requires that drug blood brain barrier (BBB) and encounter immune cells. We have previously described a mechanism which may facilitate transport CD3-engaging therapeutics into CNS, via carriage on activated T Building this, we sought to produce specific cell phenotypes rapidly enter accumulate in CNS. METHODS 8–10-week-old C57/Bl6 mice (n=5-6 per group) were implanted with 30,000 CT2AvIII cells established over 14 days. Mice received (1) CD45.1 lymphocytes IL-7 Concanavalin-A (single intravenous (IV) injection, 1 x 107 adoptive lymphocyte transfer (ALT)) or (2) IL-2 serial Con-A stimulation. sacrificed 3 hours following ALT their brains analysed flow cytometry. A follow-up timepoint 48 was also analysed. Groups compared using Mann-Whitney U test. RESULTS Ex vivo culture group yielded mixed population effector memory whereas 2 resulted terminally differentiated only. VLA-4, migratory integrin involved entry CNS upregulated group. Group demonstrated significantly enhanced CD8+ tumor bearing hemispheres 3- 48-hours administration (p = 0.005, p 0.0159 respectively). CONCLUSIONS Varying cytokine cocktail used for ex activation expansion results markedly different trafficking properties phenotype composition. Ongoing work will determine how localization affects accumulation hitchhiking mechanism. Further, evaluate safety combinatorial Phase I trials (NCT04903795) cGMP Brain Bi-specific engager (BRiTE).