UnTIL We Meet Again: Testing TIL Therapies in an Ex Vivo Platform

Tumor-infiltrating lymphocyte (TIL)-based immunotherapy is currently at the forefront of cutting-edge immuno-oncology treatments. TILs are a type of adoptive cellular therapy (ACT) using lymphocytes that are found within tumor tissues; most of these lymphocytes are T cells that can specifically target tumor cells. For TIL-based therapies, these T cells are harvested from a tumor biopsy, expanded ex vivo, and infused back into the patient. Advances in TIL-based therapies are driven by preclinical characterization and screening of TILs against a wide array of tumor types.

Consider these factors related to preclinical TIL therapy studies as you develop new research protocols:

1. Wanted Alive, Not Dead: The development of plate-based TIL assays offers users flexibility and scalability, but it is critical to assess the viability of cultured TILs at the outset of any of these assays. Some TIL cultures are prone to high levels of cell death over time, and culture conditions may need to be optimized to include different cytokines and growth factors to promote viability as well as growth and expansion of tumor-specific T cells.
   
   
2.  Cell Selection: Optimal TIL culture conditions should enhance the expansion of tumor-specific T cells but may also involve a step to deplete other cells prior to expansion. This may involve the depletion of adherent cell subsets with immunosuppressive characteristics such as myeloid-derived suppressor cells (MDSCs). Removing these cells from ex vivo culture allows TILs to expand and differentiate into T cells with tumor-specific cytotoxic activity.
   
   
3. TIL Test Drive: Ex vivo expansion of TILs must include functional assays in order to ascertain if these cells have anti-tumor properties. Analysis typically includes flow cytometry-based immunophenotyping and characterization of cytokine production and tumor-specific cytotoxicity. An ideal TIL product will show tumor-specific activity with limited off-target effects, and TILs will retain a phenotype that is predicted to be well-tolerated in a patient upon re-infusion.

Preclinical TIL studies are continuing to expand the usage of TIL-based therapies against a wide range of solid tumors, and this field of study will advance further as ex vivo culture and analysis techniques improve.