Abstract 4245: The Immune strategies to convert cold to hot tumors and overcome resistances

Abstract Cold tumors evade immunotherapy through limiting T cell priming inside draining LN or infiltration into TME. Here, we have developed sequential strategies to overcome the limitation. Firstly, we have developed new mRNA vaccine expressing membrane cytokines with shared or mutated antigens to more and better prime tumor specific T cells (TST) without toxicity. Secondly, we generated tetramer forms of NGR that fusing into Fc-pro-IL2 that selectively targeted CD13 enriched on TME for more IL-2 to rejuvenate dysfunctional T cells. Unexpectedly, cis-delivery of IL-2 on CD13 on tumor vessels can bridge the cross-talk between tumor vessels and TST. Activated T cells can remodel tumor vessels to allow more infiltration. To sustain their anti-tumor activities, we have sequentially delivered tumor-activating cytokines (pro-IL2) guided by anti-PD-1 antibody (anti-PD-1-pro-IL2) or radiation-activating TLR agonists to help DC-T cell interaction inside TME to sustain T-cell effector function. Together, we have sequential strategies converting cold to hot tumors and then simultaneously reinvigorates TIL to overcome the limitations of current immunotherapies. Citation Format: Yang-Xin Fu, . The Immune strategies to convert cold to hot tumors and overcome resistances abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4245.