BiTE-Secreting HIP Dual CAR-γδT Cells in Non-Small Cell Lung Cancer

¹ School of Life Science, Hong Kong University of Science and technology, 999077, China Hong Kong
² School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China
³ School of Life Science and Technology, China Pharmaceutical University, Nanjing, 211198, China
⁴ Second Clinical Medical College, Anhui Medical University, Hefei, 230032, China
⁵ XJTLU Wisdom Lake Academy of Pharmacy, Xi’an Jiaotong-Liverpool University, Suzhou, 215123, China

1kzhangbf@connect.ust.hk 2rogerwang@stu.cpu.edu.cn 3dengbiyou327@outlook.com 4chentianyileo@163.com 5Xuexia.Shi22@student.xjtlu.edu.cn

Abstract

Lung cancer is the most frequently diagnosed cancer globally, with non-small cell lung cancer (NSCLC) constituting approximately 85% of cases. Current treatments face challenges such as resistance to targeted therapies and adverse effects associated with immunotherapies. This study aims to enhance NSCLC treatment by utilizing BiTE-secreting hypoimmune (HIP) dual CAR-γδT cells. Building on previous research, we propose to engineer human γδT cells by knocking out B2M and CIITA genes, followed by transfection with CD47 and CAR genes. To evaluate the reduction of allorejection contributed by BiTE-secreting HIP dual CAR-γδT cells and to have a better understanding of their effects in human NSCLC, these modified cells will be injected into humanized NOD SCID IL2RgammaNULL (NSG)-bone marrow liver thymus (BLT) mice bearing A549 tumors. We will assess persistence and anti-tumor activity via bioluminescence imaging and flow cytometry. Results are expected to indicate that HIP dual CAR-γδT cells exhibit superior persistence and reduced immunogenicity, enhancing antitumor efficacy compared to control groups. Additionally, rechallenge experiments are likely to confirm prolonged effectiveness. Our findings suggest that BiTE- secreting HIP dual CAR-γδT cells will offer a promising, targeted treatment for NSCLC, combining reduced immunogenicity with potent antitumor activity.