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Adoptive cell transfer with autologous tumor-infiltrating lymphocytes (TILS) show promising overall response rates for the treatment of advanced breast cancer. In a clinical trial of 42 women with metastatic breast cancer, 28 (or 67%) generated an immune reaction against their cancer. The approach was used to treat six women, half of whom experienced measurable tumor shrinkage.1

About Tumor Infiltrating Lymphocytes

TILS are a type of adoptive cellular therapy (ACT) in which T cells are isolated based on their tumor-specific antigen recognition and then expanded outside the body and infused back into the patient.

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TILs are a collection of lymphocytes that have penetrated the stroma of a cancer and are largely comprised of T cells that are actively engaged in fighting the cancer. TIL therapy requires that a biopsy be taken of the cancer from which DNA can be isolated and sequenced to identify mutations found in the cancer. TILs that can recognize the cancer are then selected, expanded, and transfused back into the patient. TILs target tumor cells that have specific proteins on their surface, called neoantigens, that the immune cells recognize. Neoantigens are produced when mutations occur in tumor DNA.

Hormone receptor–positive breast cancers has been thought to not be capable of provoking an immune response and is therefore not susceptible to immunotherapy.  These study results suggest that immunotherapy can be used to treat some people with metastatic breast cancer who have exhausted all other treatment options.

The results of the study come from an ongoing phase 2 clinical trial that was designed to see if immunotherapy could lead to tumor regressions in people with metastatic epithelial cancers, including breast cancer. In the trial, the researchers used whole-genome sequencing to identify mutations in tumor samples from 42 women with metastatic breast cancer whose cancers had progressed despite all other treatments. The researchers then isolated TILs from the tumor samples and, in lab tests, tested their reactivity against neoantigens produced by the different mutations in the tumor. Twenty-eight women had TILs that recognized at least one neoantigen. Nearly all the neoantigens identified were unique to each patient.

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For the six women treated, the researchers took the reactive TILs and grew them to large numbers in the lab and then returned them via intravenous infusion. 

After the treatment, tumors shrank in three of the six women. One woman remains cancer free beyond 5 years and the other two women had tumor shrinkage of 52% and 69% after six months and 10 months, respectively of treatment respectively. Some disease returned and was surgically removed. Those women now have no evidence of cancer approximately five years and 3.5 years, respectively, after their TIL treatment.

Reference

https://ascopubs.org/doi/full/10.1200/JCO.21.02170