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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.

Isolation and expansion of CD137pos 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. 

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.

Intellectual Property: 

Reference Media:   

Desired Partnerships: 

  • TIL therapeutic developers
  • Research tool providers
  • CDMOs
  • Terms available upon request

Patent Information:

Inventors:

Docket : Z6725 

For Information, Contact:

Benning Wang Associate Director, Technology Licensing
University of Pennsylvania
215-573-6709
benning@upenn.edu

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