Understanding Emerging Cell Therapy in Lung Cancer

At a recent CURE Educated Patient® Lung Cancer Summit, held in tandem with the 2025 PER® New York Lung Cancer Symposium, Dr. Adam J. Schoenfeld, a thoracic medical oncologist and Complex Therapeutics Section Head at Memorial Sloan Kettering Cancer Center in New York, delivered an extensive overview of how cellular therapies are shaping the future of lung cancer care.

Schoenfeld emphasized that lung cancer is not a single disease and stressed that treatment decisions “depend entirely on the distinct biology of each tumor.” Although immunotherapy and targeted therapy have delivered meaningful progress, he noted that many individuals still require more durable strategies, particularly after disease progression.

Moreover, he focused on three major categories of adoptive T-cell therapies: tumor-infiltrating lymphocyte (TIL) therapy, T-cell receptor (TCR) therapy, and chimeric antigen receptor (CAR)-T cell therapy. Each approach uses living immune cells, created for each patient individually, to “retrain or supercharge the immune system” so it can better identify and attack cancer cells. These therapies are highly personalized, and although the manufacturing process is lengthy, they offer the possibility of lasting activity after a single infusion.

TIL Therapy: Using the Immune Cells Already Inside the Tumor

Schoenfeld described TIL therapy as an approach that “empowers an army you already have.” TILs are immune cells that have naturally migrated into a tumor but become overwhelmed. During treatment, these cells are collected from tumor tissue, expanded extensively in a laboratory, and then reinfused to boost the body’s natural immune response.

Amtagvi (lifileucel) is now the first FDA-approved T-cell therapy for a solid tumor, and lung cancer studies are advancing quickly. Early research has shown that TIL therapy is feasible and can produce durable responses in individuals whose cancer no longer responds to immunotherapy. The phase 2 IOV-LUN-202 study is enrolling patients who have progressed after chemo-immunotherapy and do not have EGFR or ALK alterations.

Common side effects result from the short chemotherapy course used before infusion and the immune activation that follows. Temporary low blood counts, infection risk, nausea, fever and fluid shifts are expected but are generally short-lived and manageable with inpatient monitoring. Most effects resolve over approximately one to three weeks, although fatigue can persist longer.

TCR Therapy: Targeting Key Cancer Mutations

TCR therapies enhance the natural “X-ray vision” of T cells, enabling them to detect cancer targets located inside tumor cells. This approach is matched to a specific tumor antigen and requires a patient to have the appropriate HLA type, which determines how the immune system presents antigens.

Schoenfeld explained that this technology opens the door to targeting “key driver mutations that traditional immunotherapy has never been able to reach.” Tecelra (afamitresgene autoleucel) became the first FDA-approved TCR therapy, and several trials are exploring TCR approaches across solid tumors. One example is NT-175, a phase 1 trial for tumors with the TP53 R175H mutation. Because alterations in TP53, KRAS, EGFR and ALK are common in lung cancer, TCR therapy may eventually become a way to immunologically target specific drivers that previously resisted immune-based strategies.

Side effects often resemble those seen with CAR-T, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Both are temporary inflammatory reactions that experienced care teams can manage with established treatments such as steroids or tocilizumab. Most individuals recover fully after the inflammation resolves.

CAR-T Therapy: Engineering “Supercharged” T Cells

CAR-T therapy attaches an antibody-derived “sensor” to a T cell, enabling it to detect targets on the surface of cancer cells without requiring a specific HLA type. These cells carry built-in costimulatory domains that help them activate and expand quickly. CAR-T cells cannot recognize targets inside tumor cells, making the identification of accurate surface markers critical in lung cancer.

Progress is advancing most rapidly in small cell lung cancer (SCLC), where DLL3 is highly expressed. Schoenfeld noted that the recent approval of DLL3-targeting bispecific antibodies “laid the groundwork for evaluating CAR-T in the same space.” Trials evaluating DLL3-directed CAR-T cells are ongoing. For non–small cell lung cancer (NSCLC), finding safe, cancer-specific surface targets has been more challenging, although early-phase studies are exploring engineered designs that may improve precision and safety.

Managing CRS and ICANS Across TCR and CAR-T Therapies

CRS results from a rapid release of cytokines and may cause fever, low blood pressure, rapid heart rate or low oxygen levels. ICANS may lead to temporary confusion, difficulty speaking, tremors or headaches. Schoenfeld emphasized that these reactions are expected, manageable and reversible for most patients.

He concluded that cell therapies represent a “new frontier of personalized, durable cancer treatment.” TIL therapy is furthest along in lung cancer, supported by early response data and an active pivotal trial. TCR and CAR-T therapies continue to evolve quickly, particularly for driver mutations and SCLC. Although these treatments involve intensive preparation and careful monitoring, their potential to harness a patient’s immune system in a more powerful and lasting way offers meaningful promise for the future.

Reference

“Cell therapy in Lung Cancer: What is it and Where are We Going?,” by Dr. Adam J. Schoenfeld. CURE Educated Patient® Lung Cancer Summit; Nov. 15, 2025; New York, New York.

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