Abstract A chimeric anti-GD2 antibody has been shown to significantly improve event-free survival of high-risk neuroblastoma. However, ∼40% of patients still relapse and succumb to disease, necessitating new strategies to improve its efficacy. We evaluated the anticancer efficacy of combining anti-GD2 with anti-PD-1 in A/J and C57BL/6 mice bearing GD2-expressing neuroblastoma NXS2 and lymphoma EL4, respectively. Immune cell profiles and expression of immunogenic cell death markers were determined by flow cytometry. We found that PD-1 blockade by i.p. injection of anti-PD-1 (100 μg/mouse) augmented anticancer efficacy of anti-GD2 (100 μg/mouse) in NXS2- and EL4-bearing mice, along with increased NKG2D+ natural killer cells in the spleen and tumor microenvironment and decreased myeloid-derived suppressive cells in the spleen. Notably, long term surviving mice after combination treatment with anti-GD2 and anti-PD-1 were protected from tumor rechallenge. Such immunological memory was mediated by CD4 and CD8 T cells, as attested by adoptive transfer studies. Mechanistically, combination of anti-GD2 with anti-PD-1 resulted in immunogenic cell death, with upregulated calreticulin, HSP70, and HSP90 on tumor cells, which elicited immunological memory response. In summary, the combination of anti-GD2 with immune checkpoint blockade can induce immunogenic cell death of tumor cells to generate tumor-specific immunological memory CD4 and CD8 T cells, leading to augmented and durable anti-cancer efficacy. Citation Format: Jung-Tung Hung, Jing-Rong Huang, Alice L. shih-Ping Chiou, Yu. Anti-GD2 combined with anti-PD1 enhances tumor immunity with T cell memory via inducing immunogenic cell death 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 B025.
Hung et al. (Wed,) studied this question.