Selective T cell repopulation for enhanced immunotherapy

This technology is a strategy for selective T cell repopulation that enhances immunotherapy by quantifying and expanding progenitor T cells within tumors and peripheral blood in conjunction with immunotherapy.

Unmet Need: Limited progenitor T cell levels hinder anti-PD-1 treatments

Although anti-PD-1 therapies have improved cancer outcomes, durable responses are limited in many patients. A key factor is the insufficient levels of progenitor T cells available to respond to checkpoint inhibitors. Therapeutic interventions involving metabolic modulation upstream of the T cell activation pathway may expand responses to existing immunotherapeutics in a broad range of cancer types and autoimmune disorders by expanding the amount of critical progenitor T cells. Additionally, measurement of progenitor T cells may help elucidate patient responsiveness to treatment.

The Technology: Strategy to reinvigorate T cells for improved anti-tumor responses

This technology identifies T cell biomarkers that can be used to determine and modulate patient responsiveness to immune checkpoint inhibitors. By measuring the number of TCF-1+ T cells in a blood or tumor sample, it can help to identify therapeutic strategies for non-responsive patients. Further, this technology offers a strategy for modulating metabolic pathways to strategically replenish T-cell populations. As such, this technology has the potential to increase the therapeutic effectiveness of immunotherapies and personalized treatments.

This technology has been validated in multiple mouse models of cancer as well as corroborated by clinical findings in a melanoma cohort, in which relative levels of the self-renewing progenitor T cells measured prior to treatment with immunotherapy predicted clinical benefit.

Applications:

• Biomarker assay for predicting immune checkpoint blockade (anti-PD-1) therapy responsiveness
• Therapeutic strategy to improve T-cell populations via metabolic modulation
• Treatment to enhance immune response to cancer immunotherapy
• Research model for T cell development and function
• Treatment for autoimmune disorders including Chron’s disease, inflammatory bowel disease, autoimmune diabetes, and lupus
• Treatment for chronic viral infections including tuberculosis, malaria, HIV, hepatitis B/C, cytomegalovirus, and Epstein-Barr virus

Advantages:

• Effective identification of target patient population
• Minimally invasive approach using collected blood samples that does not require tumor biopsy
• Treatment to expand antitumor responses in previously immune-checkpoint refractory cancers
• Applicable to a broad range of cancers and other immune-related disorders
• Optimized treatment duration to reduce toxicity

Lead Inventor:

Steven Reiner, MD

Patent Information:

Patent Pending (US20240027465)

Related Publications:

• Maniar R, Wang PH, Washburn RS, Kratchmarov R, Coley SM, Saqi A, Pan SS, Hu J, Shu CA, Rizvi NA, Henick BS, Reiner SL. Self-Renewing CD8+ T-Cell Abundance in Blood Associates with Response to Immunotherapy. Cancer Immunol Res. 2022 Dec 13:CIR-22-0524

Tech Ventures Reference:

• IR CU20336

• Licensing Contact: Devin Jones