How do bispecific antibodies and CAR T-cell therapy work for advanced non–small cell lung cancer?

Bispecific antibodies and CAR T-cell therapy are two types of immunotherapy that aim to harness the immune system to fight cancer. For advanced non–small cell lung cancer (NSCLC), these treatments are still largely experimental, but early research shows promise. Bispecific antibodies are engineered to bind to two targets at once—one on the cancer cell and one on an immune cell—bringing them together to kill the tumor. CAR T-cell therapy involves removing a patient's own immune cells, genetically modifying them to recognize cancer, and infusing them back. Both approaches are being studied to overcome resistance to standard treatments like checkpoint inhibitors.

What the research says

Bispecific antibodies have shown favorable efficacy and safety in lung cancer, according to a 2026 review ¹⁰. One example is amivantamab, a bispecific antibody that targets EGFR and MET, which is FDA-approved in combination with lazertinib for first-line treatment of EGFR-mutant advanced NSCLC ⁷. Another approach uses T cells engineered to secrete bispecific T-cell engagers (TCEs); a 2024 study showed that tumor-infiltrating lymphocytes (TILs) engineered to secrete anti-EGFR × anti-CD3 TCEs induced regression of patient-derived NSCLC xenografts in mice ⁹. This strategy, called STAb-T therapy, aims to improve tumor reactivity by having T cells produce their own bispecific antibodies locally ⁹.

CAR T-cell therapy for NSCLC faces more hurdles. A 2026 review notes key challenges including on-target, off-tumor toxicity (where CAR T cells attack healthy tissues), cytokine release syndrome (a dangerous immune overreaction), limited T-cell persistence, insufficient tumor trafficking, and an immunosuppressive tumor microenvironment ¹⁰. While CAR T has been highly successful in blood cancers, solid tumors like NSCLC present additional barriers. However, advances in CAR design and delivery methods may broaden its applicability ¹⁰. A 2024 review highlights that next-generation immunotherapies, including novel CAR designs, are being developed to overcome resistance mechanisms to PD-1 blockade, such as failure in antigen presentation and an immunosuppressive tumor microenvironment ¹¹.

Currently, bispecific antibodies are more advanced in clinical use for NSCLC, with approved combinations like amivantamab plus lazertinib ⁷. CAR T-cell therapy remains investigational, with ongoing research focused on improving safety and effectiveness ¹⁰¹¹.

What to ask your doctor

• Are there any clinical trials of bispecific antibodies or CAR T-cell therapy for my type of advanced NSCLC?
• What are the potential side effects of these treatments, such as cytokine release syndrome or damage to healthy organs?
• How do these therapies compare to standard treatments like checkpoint inhibitors or targeted therapy for my specific cancer mutations?
• If I have an EGFR mutation, is amivantamab (a bispecific antibody) an option for me?
• What is the current evidence for CAR T-cell therapy in lung cancer, and are there any approved options?