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CD8 TIL adoptive cell therapy (4-1BB+CD25+ subset) is an experimental adoptive cellular immunotherapy developed by researchers at the Providence Cancer Institute. This therapy utilizes a highly potent and tumor-reactive subset of CD8+ tumor-infiltrating lymphocytes (TILs). These cells are initially isolated from the tumor microenvironment based on the expression of CD39 and CD103 (double-positive population) and are further selected by identifying a subset that upregulates 4-1BB (CD137) and CD25 (IL-2 receptor alpha) upon exposure to autologous tumor cells. This specific subset, representing approximately 5-10% of the double-positive TILs, demonstrates significantly higher interferon-gamma production and superior anti-tumor efficacy compared to the parental population. Preclinical studies presented at the AACR 2026 meeting showed that these expanded cells could completely regress melanoma brain metastases in xenograft models, whereas the broader TIL population failed to control tumor growth. This approach aims to improve the efficacy of TIL therapy for patients with advanced or recurrent cancers, particularly those with central nervous system involvement.
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