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

A platform to isolate and expand CD137-positive (CD137pos) 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 CD137pos TILs can cause significant reduction in tumor size and higher IFN-λ secretion, indicating that isolation and expansion of CD137pos+ 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 CD137pos 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 CD137pos 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 CD137pos TIL-treated mice relative to CD137neg (p=0.016) and non-manipulated TIL groups (p=0.0354).
  • CD137 enriched TILs demonstrate significantly higher IFN-λ secretion than CD137neg 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.  

Website

https://upenn.technologypublisher.com/technology/48542

Contact Information

TTO Home Page: https://upenn.technologypublisher.com

Name: Benning Wang

Title: Associate Director, Technology Licensing

Department: Parker Institute for Cancer Immunotherapy

Email: benning@upenn.edu

Phone: 215-573-6709