This technology is an immunotherapy approach that targets the cell surface marker CD58 to enhance antitumor immunity and bypass immune evasion mechanisms, therefore improving treatment outcomes in patients.
Unmet Need: Addressing cancer immunotherapy resistance and immune evasion
Despite the success of immune checkpoint inhibitors in treating cancer, many patients develop resistance, diminishing the overall effectiveness of these therapies. Current treatments often fail to address immune evasion mechanisms and disruptions in critical pathways. Additionally, there is a pressing need for reliable biomarkers to identify which patients are likely to respond to treatment. Overcoming these resistance mechanisms will improve the precision and impact of cancer immunotherapies.
The Technology: Modulating CD58 to overcome cancer immunotherapy resistance
This technology targets CD58 to overcome cancer immunotherapy resistance. By modulating CD58 expression, it directly addresses key resistance mechanisms, such as defects in the IFNγ-JAK/STAT pathway, impaired antigen presentation, and immune evasion. Additionally, this approach identifies important gene signatures related to immune fitness therefore offering biomarkers for optimizing patient selection and therapy customization. By directly targeting CD58, this technology enhances the efficacy of immunotherapies and enables the development of combination treatments to overcome therapeutic resistance.
This technology has been validated in patient-derived melanoma co-cultures and autologous tumor-infiltrating lymphocyte co-cultures.
Applications:
- Immunotherapy for cancer
- Prevention of immunotherapy resistance in various cancer types
- Screening for immunotherapies
- Biomarker for prediction of response to immunotherapy
- Research tool for analysis of mechanisms guiding cell chirality
Advantages:
- Improved response rates in patients resistant to checkpoint inhibitors
- Compatible with utilization as a combination therapy
- High-throughput platform for identifying key resistance pathways
- Broad applicability across different cancers
Lead Inventor:
Benjamin Izar, MD, Ph.D.
Patent Information:
Patent Pending(US20240294643)
Related Publications:
Frangieh CJ, Melms JC, Thakore PI, Geiger-Schuller KR, Ho P, Luoma AM, Cleary B, Jerby-Arnon L, Malu S, Cuoco MS, Zhao M, Ager CR, Rogava M, Hovey L, Rotem A, Bernatchez C, Wucherpfennig KW, Johnson BE, Rozenblatt-Rosen O, Schadendorf D, Regev A, Izar B. “Multimodal pooled Perturb-CITE-seq screens in patient models define mechanisms of cancer immune evasion.” Nat Genet. 2021 Mar; 53(3): 332-341.
Melms JC, Ho P, Rogava M, Izar B. “From patient tissue correlates to molecular mechanisms of cancer immune evasion: the emerging role of CD58 and PD-L1 co-regulation via CMTM6.” Genes Immun. 2024 Feb; 25(1): 82-84.
Ho P, Melms JC, Rogava M, Frangieh CJ, Poźniak J, Shah SB, Walsh Z, Kyrysyuk O, Amin AD, Caprio L, Fullerton BT, Soni RK, Ager CR, Biermann J, Wang Y, Khosravi-Maharlooei M, Zanetti G, Mu M, Fatima H, Moore EK, Vasan N, Bakhoum SF, Reiner SL, Bernatchez C, Sykes M, Mace EM, Wucherpfennig KW, Schadendorf D, Bechter O, Shah P, Schwartz GK, Marine JC, Izar B. “The CD58-CD2 axis is co-regulated with PD-L1 via CMTM6 and shapes anti-tumor immunity.” Cancer Cell. 2023 Jul 10; 41(7): 1207-1221.
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