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

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 N...

Full description

Saved in:
Bibliographic Details
Main Authors: Zhang Kaiheng, Wang Mufeng, Deng Biyou, Chen Tianyi, Shi Xuexia
Format: Article
Language:English
Published: EDP Sciences 2025-01-01
Series:BIO Web of Conferences
Online Access:https://www.bio-conferences.org/articles/bioconf/pdf/2025/25/bioconf_icbb2025_02008.pdf
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2117-4458