University of Pittsburgh researchers have developed a novel approach for isolating and expanding tumor-infiltrating γδ T cells (TILs) from solid tumors, presenting a significant advancement in immunotherapy. This new method overcomes the limitations of conventional αβ T cell receptor (TCR)-based therapies, which rely on MHC-restricted antigen recognition and are subject to immune escape. The expansion of γδ T cells, which can recognize tumor-specific non-peptide antigens independently of MHC, has shown potential to enhance antitumor activity and provide better outcomes for patients with various solid tumors.

Description

This invention involves a protocol for the isolation and rapid expansion of tumor-infiltrating γδ T cells (γδ TILs) from patient tumor fragments. These cells are expanded using a novel method in a clinical-scale environment. The γδ TILs exhibit an activated tissue-resident memory phenotype and maintain strong antitumor properties without the need for MHC restriction, thereby enhancing their potential in adoptive cell therapy.

Applications

• Cancer Immunotherapy
• Treatment of Solid Tumors
• Research in Cellular Therapies
• Enhancing Adoptive Cell Therapy Protocols

Advantages

This innovative approach to expanding tumor-infiltrating γδ T cells offers multiple advantages over conventional TIL therapies. γδ TILs can target tumors independently of MHC expression, reducing the risk of immune escape, and demonstrate superior tumor reactivity compared to αβ T cells. The rapid and efficient expansion protocol allows for clinical-scale production, enhancing the feasibility of this therapy in clinical settings. Additionally, γδ TILs exhibit innate tissue residency, which improves their ability to traffic to and persist within tumor sites, potentially leading to more effective and durable therapeutic responses.

Invention Readiness

The invention is currently supported by in vitro data demonstrating the successful isolation and expansion of γδ TILs from resected solid tumors. γδ TILs displayed a tissue-resident memory phenotype and were selectively expanded. The resulting γδ TIL cultures showed minimal contamination by other cell types (less than 2% NK cells and less than 5% αβ T cells) and exhibited strong antitumor reactivity, independent of MHC expression. Furthermore, expanded γδ TILs demonstrated a significant effector memory phenotype and maintained the expression of co-stimulatory and natural cytotoxicity receptors, highlighting their suitability for clinical-scale adoptive cell therapy.

IP Status

https://patents.google.com/patent/US20230117388A1

Producing Tumor Infiltrating T Cells for Immunotherapy