A platform to isolate and expand CD137-positive (CD137^pos) tumor-infiltrating lymphocytes (TILs) to use in adoptive immunotherapy and translational studies.

Adoptive immunotherapy using either naturally occurring or genetically modified tumor-infiltrating lymphocytes (TILs) is being developed to treat solid tumors clinically. However, methods for isolating and expanding the subset of tumor-reactive TILs for high selectivity and reactivity are yet to be optimized. 

The Powell Lab showed that CD137^pos TILs can cause significant reduction in tumor size and higher IFN-λ secretion, indicating that isolation and expansion of CD137^pos+ TILs can yield a TIL product of high selectivity and reactivity.

The method includes incubation of enzymatically digested tumors with pro-survival cytokines interleukin (IL)-7 and IL-15, which maintain CD137 expression in the TIL population, followed by CD137 enrichment. The tumor-reactive CD137^pos TILs can be enriched using positive magnetic bead separation and cultured in the presence of cytokines such as IL-2. Compared to non-enriched TILs, expanded and enriched CD137^pos TILs show enhanced autologous tumor reactivity in vitro and antitumor activity in mice bearing human tumors. 

• This method is cost-effective and can be integrated easily into cell production platforms of choice.
• A significant reduction in tumor size was observed in CD137^pos TIL-treated mice relative to CD137^neg (p=0.016) and non-manipulated TIL groups (p=0.0354).
• CD137 enriched TILs demonstrate significantly higher IFN-λ secretion than CD137^neg TIL subsets selected with other biomarkers such as PD-1, CD103 or CD139.