Developing CAR-T/NK cells that target EphA2 for non-small cell lung cancer treatment

Seok Min Kim ¹ Soo Yun Lee ¹ Eun Kyung Kim ^2,3 Ji Yeong Bae ² Jin Tae Hong ³ Hyo- Young Chung ^2* Tae-Don Kim ^1,4*

• ¹ Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
• ² Osong Medical Innovation Foundation, Cheongju, North Chungcheong, Republic of Korea
• ³ College of Pharmacy, Chungbuk National University, Cheongju, North Chungcheong, Republic of Korea
• ⁴ Department of Functional Genomics, KRIBB School of Bioscience, Korea University of Science and Technoloty(UST), 217 Gajeong-ro, Yuseong-gu, Deajeon, 34113, Republic of Korea

Chimeric antigen receptor (CAR) immunotherapy has revolutionized anticancer therapy, as it accurately targets cancer cells by recognizing specific antigens expressed in cancer cells. This innovative therapeutic strategy has attracted considerable attention. However, few therapeutics are available for treating non-small cell lung cancer (NSCLC), which accounts for most lung cancer cases and is one of the deadliest cancers with low survival rates. In this study, we developed a new antibody targeting erythropoietin-producing hepatocellular carcinoma A2 (EphA2), which is highly expressed in NSCLC, and established CAR-T/ natural killer (NK) immune cells to verify its potential for immune cell therapy. We found that EphA2 CAR-T cells exhibited superior killing capacity, cytokine secretion, solid tumor growth inhibition, and tumor infiltration against lung cancer cells compared to normal T cells. The anticancer efficacy of the developed EphA2 CAR-NK cells was confirmed. Therefore, our results suggest that CAR-T/NK cell targeting of EphA2 may be an effective immune cell therapy for lung cancer, particularly for NSCLC with high EpA2 expression.