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Why Research Matters with Lilit Karapetyan, MD, MS

Tumor infiltrating lymphocyte expansion from core biopsies

The overall survival of patients with melanoma drastically improves with a type of treatment called immunotherapy (IO), which activates the body’s immune system to fight cancer more effectively. However, despite many recent advancements in IO development, such treatment fails many patients. Tumor infiltrating lymphocyte (TIL) therapy represents a promising approach for the treatment of melanoma patients whose disease does not benefit from conventional immunotherapy agents. Initial promising studies led to the TIL therapy approval by the US Food and Drug Administration for previously treated patients with unresectable or metastatic melanoma. In the current practice patients undergo surgery and collected tumor from a patient during surgery is used for TIL growth in the laboratory. After TILs grow billions in number and meet all criteria for release, they are infused back into the patient to attack the cancer cells.

This study investigates whether TILs can be successfully grown from core needle biopsies rather than surgical samples. Patients receiving a core needle biopsy as part of their clinical care will have additional passes of the needle into the tumor. This procedure is usually being done by interventional radiologist under imaging guidance and does not require any open surgery. The tissue removed from the tumor by a hollow needle, called core, is then grown in laboratory. Additionally, this study investigates how specific pathological and immunological characteristics of tissue impact quality of generated TIL. Finally, we use additional molecules along with interleukin-2 in the laboratory to support growth rate of TIL and number of “good” lymphocytes in the TIL product. We believe that this work will lead to a novel approach in optimizing TIL growth from patient core biopsy samples which may facilitate and improve TIL therapy outcomes including providing better quality of life for patients and the avoidance of surgical excision. This study also provides an opportunity to optimize growth from unresectable lesions, which would otherwise be considered as non-harvestable tumor sites which would disqualify patient’s accrual on TIL-based therapy trials or standard of care TIL therapy. From a tiny piece of tissue, smaller than a grain of rice, millions of TILs can be grown in a month!