Abstract B023: Activation of antigen-specific CD8 T cells using nano-scale artificial antigen-presenting cells promotes tumor vessel normalization to potentiate different cancer treatments

Dysfunctional tumor blood vessels restrict the infiltration of immune cells, perfusion of immune checkpoint antibodies, and chemotherapeutic drugs in the solid tumor microenvironment (TME), which leads to the sub-optimal therapeutic outcomes. We developed nanoscale artificial antigen-presenting cell (aAPC) displaying p-MHCs and co-stimulatory molecules that engage and expand both adoptively transferred and low-frequency endogenous tumor antigen-specific CD8 T-cells in tumor-bearing animals and normalize the structural architecture of the tumor blood vessels, enhancing the infiltration of immune cells and therapeutic efficacy of immuno- and chemo-therapy. We evaluated the functional activity of aAPC in the murine melanoma model, including ovalbumin-expressing B16-F10 (Ova-B16-F10). Animals carrying the Ova-B16-F10 tumor received OT-I CD8 T-cells and subsequently treated with Ova-aAPC showed delayed tumor growth, which correlated with the peripheral expansion of antigen-specific CD8 T-cells and infiltration of immune cells, including antigen-specific CD8 T-cells in the TME, identified by the p-MHC tetramer in FACS analysis. Next, we further dissected the structural architecture of the tumor blood vessel using confocal microscopy, and inspiringly, we found that enhanced pericyte coverage over endothelial cells, indicating the integrated structure of the tumor blood vessels. Furthermore, we observed enhanced expression of VE-Cadherin on the endothelial cells harvested from TME using FACS, strongly suggesting excellent structural integrity of the blood vessel. To ascertain this result, we performed the Evans blue leakiness test and found that the aAPC-treated group showed a significant reduction of tumor blood vessel leakiness. Improved pericyte coverage and lesser vessel leakiness resulted in decreased expression of hypoxia inducible factor-1α (HIF-1α) in the TME. Taken together, it is evident that administration of aAPC can normalize the tumor blood vessels. We examined the capacity of aAPC displaying mTRP2(180-188)-Kb and anti-CD28 to activate endogenous tumor-reactive CD8 T cells for inhibiting the growth of B16-F10 melanoma. Indeed, we found that these aAPCs could promote the infiltration of mTRP2(180-188)-Kb specific CD8 T-cells in the TME by normalizing the tumor blood vessel with improved pericyte coverage, reduced HIF-1α expression, and decreased vessel leakiness. We further investigated whether it improves the therapeutic efficacy of immune checkpoint antibodies and chemotherapeutic drugs. Inspiringly, we found that animals receiving aAPC treatment showed enhanced therapeutic efficacy of drugs/antibodies despite the tumor growth at the advanced stage. Interestingly, without aAPC treatment at that advanced stage of tumor, animals did not respond to the chemotherapeutic drugs and antibodies. Collectively, these findings offer aAPC-mediated therapeutic platform capable of promoting the antigen-specific T-cell activation and expansion to enhance the therapeutic efficacy by synergizing the chemo and immunotherapy to treat solid tumors. Citation Format: FAISAL JAMAL, Arpita Das, Arnab Kumar. Sahoo, Antara Mondal, Khushboo Chaudhary, Santiswarup Singha. Activation of antigen-specific CD8 T cells using nano-scale artificial antigen-presenting cells promotes tumor vessel normalization to potentiate different cancer treatments [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B023.