T-Cell Therapies Offer New Ways to Treat Lung Cancer

The immune system can recognize and destroy abnormal cells, but lung cancer can develop ways to avoid recognition. T-cell redirecting therapies aim to overcome immune escape by helping T cells recognize and target cancer cells.

The challenge is that cancers can behave differently from one patient to another.

Cancer heterogeneity refers to biological differences within and between tumors that can influence how cancer responds to treatment. Cancer cells can also change over time and find ways to continue growing or hide from the immune system, which Dr. Gonzalez-Velez, a medical and thoracic oncologist at Hackensack University Medical Center described as “escape mechanisms.”

How could T-cell therapies work against lung cancer?

T cells are immune cells that can recognize and destroy abnormal cells. T-cell redirecting therapies are designed to help T cells identify cancer cells or bring T cells closer to their targets.

The goal fits into a broader move toward individualized cancer treatment. Proteins, genetic changes and other biomarkers found in a tumor can sometimes help identify treatments designed to target specific characteristics of the cancer.

“The basic idea is that cancer has different proteins, and if you have the yellow protein, you get the yellow medication. If you have the red protein, you get the red medication,” Gonzalez-Velez said.

Matching a treatment to a cancer is more complicated in practice. A useful target may not exist for every cancer, and tumors can change during treatment. Depending on the cancer, treatment may involve chemotherapy, immunotherapy, targeted therapy, cellular therapy or a combination of treatments.

Why does the tumor microenvironment matter in lung cancer?

Cancer cells do not grow in isolation because a tumor exists within a tumor microenvironment, which includes immune cells, normal tissue and other structures surrounding the cancer.

He compared a tumor and its surroundings to a house within a neighborhood. Normal tissue forms part of the structure, while components of the immune system act like the plumbing and electricity.

The tumor microenvironment can influence how the immune system responds to cancer. Some treatments focus not only on cancer cells but also on activating parts of the immune system around the tumor.

“Sometimes we don't only attack the cancer itself,” Gonzalez-Velez said.

T-cell therapies build on the same concept by using components of the immune system to recognize and target cancer cells.

Why are T-cell therapies being studied in small cell lung cancer?

Small cell lung cancer (SCLC) is an aggressive form of lung cancer that has experienced years of limited treatment advances.

“There has been a multi-year gap of very little research, but now finally, in the last few years, and in the coming years, we will be making some advances in new therapies for small cell lung cancer,” he said.

Tarlatamab is one example of a T-cell redirecting treatment used in SCLC. The drug is a T-cell engager that targets DLL3, a protein commonly found on SCLC cells. Tarlatamab is designed to bring T cells and cancer cells carrying DLL3 together, helping the immune system recognize the cancer cells.

Gonzalez-Velez also conducted research examining tarlatamab among patients treated outside the clinical trials that helped establish the therapy. Real-world studies can provide additional information about how a treatment performs when used in everyday cancer care.

What could T-cell research mean for patients with lung cancer?

T-cell therapies add another potential way to treat lung cancer based on characteristics of an individual tumor.

Gonzalez-Velez hopes cellular therapies and antibody-drug conjugates (ADCs) will advance cancer treatment over the next five to 10 years. ADCs use an antibody to help deliver a cancer-killing drug to cells carrying a specific target. Cellular therapies can use or modify components of a patient’s immune system to help recognize cancer. Other approaches can also activate the immune system, including vaccines, proteins that boost immune activity and strategies involving the tumor microenvironment.

Not all strategies are expected to work for every cancer. A growing understanding of the biological differences among cancers has created multiple ways to approach treatment.

“We understand now that different cancers need to be attacked in different ways,” Gonzalez-Velez said.

T-cell therapies could add another way to match the biology of a patient's lung cancer with a treatment designed to target it.

References

1. Zhao J, Bangolo A, Zhang L, Gonzalez-Velez M. T-cell redirecting therapies in lung cancer - a comprehensive analysis of clinical trials. Front Immunol. 2026;17. doi:10.3389/fimmu.2026.1917770.
2. Bangolo A, Zhang L, Gill S, et al. Real-world efficacy and safety of tarlatamab in small cell lung cancer (SCLC) and extrapulmonary small cell carcinoma (EPSCC): a single-center experience. J Clin Oncol. 2026;44(16 suppl). doi:10.1200/JCO.2026.44.16_suppl.e20127.

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