CD137 enrichment of tumor-specific tumor-infiltrating lymphocytes (TILs)

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

Problem:

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.

Solution:

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.

Technology:
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.

Advantages:

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.

Stage of Development:

Process and related reagents including the use of this technology are now available through a leading cell manufacturing system and reagent provider.
Clinical applications in development.

Isolation and expansion of CD137^pos TILs from clinical tumor samples. After the enzymatic digestion of tumor samples, CD137 expression among TILs can be increased by overnight incubation with IL-7 and IL-15. Magnetically captured/sorted CD137pos can be used in adoptive cell therapy and downstream translational studies such as the sequencing of T-cell receptor-coding genes, identification of novel tumor-associated antigens and molecular phenotyping of specific TIL subsets.

Intellectual Property: