Asset/Technology Type
New Therapeutic Strategy
Description of Invention
The invention includes compositions and methods of delivering therapeutic anti-tumor T cells by forcing them to overexpress interferon regulatory factor (IRF4) as a treatment for various solid tumors, including but not limited to melanoma, lymphoma, and colon cancer. The inventors have discovered that IRF4 is a master transcriptional determinant of anti-tumor T cell function. Increased expression of IRF4 in therapeutic T cells suppresses cancer growth by promoting tumor infiltration and effector function of both therapeutic and endogenous anti-tumor T cells.
Stage of Development
In vitro: Microarray and ChIP analyses revealed that IRF4 ablated CD4+ T cells displayed increased exhaustion and anergy signatures including PD-1, CD160, CD73, and folate receptor 4, suggesting that IRF4 plays a distinct role in preventing CD4+ T cell dysfunction. IRF4 can be overexpressed in T cells via retroviral or lentiviral transduction to induce anti-tumor effects. Latest discoveries in the references below.
In vivo: Adoptive transfer of IRF4-engineered T cells suppressed tumor growth in murine melanoma, colon and prostate cancer models. Mice which were administered IRF4-engineered T cells in combination with anti-PDL1 immunotherapy demonstrated superior anti-tumor efficacy compared to either therapy alone. IRF4 can be co-expressed in both a CD19 and PSMA CART therapy to enhance expansion and potentially anti-cancer activity.
References:
Zou D. et al., Nature Immunology volume 25, pages 66–76 (2024)
Yan H. et al., iScience, Vol 26, Issue 11, 17 Nov 2023, 108087
Yu A. et al., Research 17 Nov 2023 Vol 6 Article ID: 0271
Competitive Landscape
Currently, the most potent immunotherapies for solid tumors are immune checkpoint blockades, such as antibodies against PD-1/PD-L1 or CTLA-4. Unfortunately, these immunotherapies only partially and transiently reverse the "dysfunction" of a small subset of tumor-reactive T cells and are only effective in 20-30% of cancer patients. A major factor driving the resistance to immune checkpoint inhibitors is the lack or paucity of tumor T cell infiltration. The disclosed therapeutic approach addresses this limitation by directly modulating this functional impairment through the expression of IRF4.
Competitive Advantages:
- Enhances the patient’s own immunity
- Reduced solid tumor growth/enhanced solid tumor regression, i.e. increased survival outcomes of solid tumor patients
- Applicable across various solid tumor indications
- Decreased doses of toxic chemotherapy when used as a combination therapy
Intellectual Property (HM Ref. OTT201714)
US 12,115,190 patent issued on October 15, 2024. Published continuation patent application is pending.
Inventors
Wenhao Chen, PhD and Xian Li, PhD (Houston Methodist)
Contact Us
For more information, contact the Office of Technology Transfer at OTT@HoustonMethodist.org
