Establishment of whole tumor cell antigen-induced cellular immunotherapy for lung adenocarcinoma

Abstract Objectives Although immunotherapy improves the prognosis of many current advanced malignancies, many patients still do not respond or develop resistance after immunotherapy. The key point of cancer immunotherapy is whether the immune system can recognize the tumor as a foreign body. However, lung adenocarcinoma (LUAD) is a tumor with weak immunogenicity, and many patients do not benefit from immunotherapy. This study aimed to optimize the adoptive cell immunotherapy process and propose a new pipeline for LUAD immunotherapy. Methods This study optimized the process of adoptive cell immunotherapy by adding individualized and enhanced whole tumor cell antigens (WTCAs) modified by chemotherapeutics, irradiation, or freezing. Venous blood from lung adenocarcinoma patients was collected to extract peripheral blood mononuclear cells (PBMCs). This study also verified the efficacy of the new strategy for LUAD immunotherapy by Flow Cytometry analysis, EdU proliferation assay, Annexin V-FITC/PI apoptosis assay, and Animal models in vivo and in vitro , etc. Results WTCAs could enhance the proliferation of immune-effective CD8 + cells and inhibit the apoptosis of immune-effective CD8 + cells, especially for X-ray-induced WTCA. The efficacy of WTCAs-induced cell immunotherapy for LUAD in vitro and vivo was prominent. Tumor size was significantly reduced by adoptive cell immunotherapy, whether specific or non-specific. In contrast, WTCAs-induced immune cells induced by 4 Gy X-ray irradiation or high-dose cisplatin (10 μg/mL) had a more effective tumor inhibition capability than all other groups (p<0.001). Conclusion The adoptive tumor-specific immune cells activated by X-ray-induced WTCA could elicit the most effective tumor inhibition. This study provides new ideas for future individualized cell immunotherapy of LUAD.