Abstract 4279: FAK inhibitor APG-2449 induces immunogenic cell death and enhances anti-tumor immunity in cervical cancer through the PERK-eIF2α pathway

The focal adhesion kinase (FAK) inhibitor APG-2449, a multi-target tyrosine kinase inhibitor that also targets ALK and ROS1, has demonstrated significant potential for inducing anti-tumor immunity. In this study, we explored the effects of APG-2449 on cervical cancer, emphasizing its capacity to induce immunogenic cell death (ICD) and stimulate immune responses via the PERK-eIF2α pathway. Our findings indicate that APG-2449 enhances ATP release and calreticulin (CRT) exposure on the surface of tumor cells, which are key indicators of ICD. Moreover, treatment with APG-2449 led to a notable increase in dendritic cell (DC) maturation and promoted their differentiation into classical dendritic cells (cDCs), which are essential for antigen presentation and the subsequent activation of T-cells.In vitro co-culture models, APG-2449 effectively boosted the activation of DCs and increased the frequency of tumor-specific CD8+ T cells. These observations underscore that APG-2449 elicits a robust immunogenic response, suggesting that inhibition of FAK/ALK/ROS1 could be a promising therapeutic approach for enhancing anti-tumor immunity in cervical cancer.These results highlight the potential of APG-2449 as an innovative therapeutic agent capable of modifying the tumor microenvironment to foster an effective anti-tumor immune response via the FAK/PERK-eIF2α axis. Future studies are needed to determine the clinical efficacy of APG-2449, particularly in combination with other immunotherapies. Citation Format: Lin Zhang, Mingyue Zhang, Weihan Kang, Jing Xiao, Maple Tse, Yong Du, Dajun Yang. FAK inhibitor APG-2449 induces immunogenic cell death and enhances anti-tumor immunity in cervical cancer through the PERK-eIF2α pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4279.