SUMMARY OF INVENTION
Preferentially Expressed Antigen in Melanoma (PRAME) represents an ideal target for cancer immunotherapy as a cancer-testis antigen with restricted expression in normal tissues but broad overexpression across multiple cancer types. MSK investigators have developed a T-cell receptor mimic (mTCR) antibody called Pr20 that recognizes the PRAME ALY peptide in complex with HLA-A*02, enabling targeting of this previously “undruggable” intracellular protein.
The Pr20 antibody has been validated both as a standalone therapeutic antibody and as the targeting domain for chimeric antigen receptor (CAR) T-cell therapy. In acute myeloid leukemia (AML), PRAME mTCR CAR T-cells demonstrate potent, target-specific cytolytic activity against PRAME+/HLA-A2+ AML cell lines and primary patient samples. Preclinical studies show deep leukemia clearance and significantly improved survival in xenograft models. The technology offers dual therapeutic modalities: antibody-based therapy for redirected immune-mediated cytolysis and CAR T-cell therapy for adoptive cellular immunotherapy.
ADVANTAGES
- High specificity and safety profile: PRAME expression restricted to reproductive tissues in normal adults, with no expression detected in normal hematopoiesis.
- Validated target across cancer types: PRAME overexpressed in melanoma, neuroblastoma, breast, ovarian, cervical, lung cancers, and hematologic malignancies.
- Enhanced by combination therapy: IFN-γ treatment increases PRAME/HLA-A2 expression and may enhance therapeutic efficacy.
- Demonstrated preclinical efficacy: Complete tumor clearance in responsive xenograft models with significant survival benefit.
MARKET OPPORTUNITY
PRAME is overexpressed in a substantial subset of childhood and adult AML, with particularly high expression in t(8;21) AML subtype. The broad expression of PRAME across multiple cancer types, including melanoma, neuroblastoma, breast, ovarian, cervical, and lung cancers, presents a significant market opportunity beyond hematologic malignancies. AML represents a critical unmet medical need with cure rates of only ~10% in relapsed/refractory patients. Current CAR T-cell approaches in AML face limitations due to lack of AML-specific targets. The PRAME mTCR platform addresses these limitations by targeting a cancer-specific antigen absent in normal hematopoiesis.
PATENT INFORMATION
Strong patent portfolio, including issued patents in the US (11,384,144) with other international applications issued or pending
LEAD INVESTIGATOR
David A. Scheinberg, MD, PhD - Vincent Astor Chair and Chairman, Center for Experimental Therapeutics, Deputy Director for Therapeutic Discovery, Sloan Kettering Institute, MSK
PUBLICATIONS
- Kirkey, D.C., et al. (2023) ” Therapeutic targeting of PRAME with mTCRCAR T cells in acute myeloid leukemia.” Blood Advances
- Chang, A.Y., et al. (2017) “A therapeutic T cell receptor mimic antibody targets tumor-associated PRAME peptide/HLA-I antigens.” J Clin Invest.
CONTACT INFORMATION
James Delorme, PhD
Senior Licensing Manager
E-mail: delormej@mskcc.org