Rewiring the Immune Response in Lung Cancer: Current Progress in Bispecific Antibodies, Car-T Therapy, and the Rise of in vivo CAR-T Platforms

Authors

• Lei He
• Yi Sun
• Bowen Ma
• Guojun Lang
• Jianguo Wen
• George R Blumenschein
• Hong Ma

Language

English

Publication Date

1-1-2026

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2026.1772428

PMID

42093990

PMCID

PMC13139153

PubMedCentral® Posted Date

4-21-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Lung cancer remains the leading cause of cancer mortality worldwide and continues to impose a major clinical burden, particularly in advanced non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although targeted therapies, antiangiogenic agents, immune checkpoint inhibitors, and antibody-drug conjugates have improved outcomes in selected patients, durable responses remain limited by primary and acquired resistance. Here, we comprehensively review recent progress in immunologically oriented therapeutic strategies for lung cancer, focusing on bispecific antibodies, chimeric antigen receptor (CAR) T-cell therapy, and emerging in vivo CAR-engineering modalities. We further elaborate on the clinical rationale, latest translational and early clinical evidence, and key challenges, including on-target, off-tumor toxicity, cytokine release syndrome, limited T-cell persistence, insufficient tumor trafficking, and immunosuppression within the tumor microenvironment. Taken together, we find that while bispecific antibodies currently show favorable efficacy and safety in lung cancer; advances in CAR design and in vivo delivery may broaden the applicability of CAR-T therapy in this setting.

Keywords

Humans, Antibodies, Bispecific, Lung Neoplasms, Immunotherapy, Adoptive, Receptors, Chimeric Antigen, Animals, Tumor Microenvironment, T-Lymphocytes, Carcinoma, Non-Small-Cell Lung, Antineoplastic Agents, Immunological, Small Cell Lung Carcinoma, bispecific antibody, CAR T-cell therapy, in vivo CAR programming, lung cancer, mRNA, non–small cell lung cancer, small cell lung cancer

Published Open-Access

yes

Recommended Citation

He, Lei; Sun, Yi; Ma, Bowen; et al., "Rewiring the Immune Response in Lung Cancer: Current Progress in Bispecific Antibodies, Car-T Therapy, and the Rise of in vivo CAR-T Platforms" (2026). Faculty, Staff and Student Publications. 1018.
https://digitalcommons.library.tmc.edu/uthshis_docs/1018