Pan-Cancer Reactive NDC80 CAR


Pan-Cancer Reactive NDC80 CAR



The lack of known cancer-specific cell surface proteins has limited the development of new CAR T-cell therapeutics. Moreover, targets are often limited to a single cancer subtype which restricts the number of patients that could benefit from this modality. To identify a CAR T-cell target with broad expression across both hematologic and nonhematologic cancers, MSK investigators performed computational analyses on HLA-A*02:01 presented peptides from multiple cancer cell lines. Analysis of shared biological functions between the cell lines identified an abundantly presented NDC80 peptide. NDC80 has previously shown to be: 1) implicated in aneuploidy and tumorigenesis, 2) highly expressed across several tumors, and 3) correlated with tumor grade and prognosis, making it a desirable oncology target.

To address this target, investigators collaborated with Eureka Therapeutics to develop an NDC80 TCR-mimic CAR (NDC80 CAR). During this process, NDC80 CARs were characterized until a lead candidate was selected that killed all cancer cell lines in both a dose-dependent and target-specific manner. The lead candidate was then evaluated in vivo in leukemia and mesothelioma tumor models and benchmarked to MUC16-targeting CAR-T cells. In both models, the lead NDC80 CAR led to profound improvements over the MUC16 control, with 100% of rodents alive at 60-days compared to 0% of the MUC16 control in the mesothelioma model. The lead optimized NDC80 CAR is available for license  and could enable a therapeutic approach to target multiple cancer subtypes.


NDC80 is highly expressed across hematologic and non-hematologic cancers and enables targeting of:

  • Oncogene expressing cancer cells- overexpression of NDC80 shown to be associated with tumor formation in an inducible rodent model (Diaz-Rodríguez et al., 2008).
    • Limits potential for tumor escape by downregulation of NDC80.
  • Multiple cancer types- NDC80 peptide was detected in >90% of A*02+ cancer cell lines.
    • Mass spectrometry analysis of cancer cell lines suggests that the NDC80 CAR may be active against both hematologic (ex: AML, B-ALL, multiple myeloma, DLBCL) and nonhematologic (ex: melanoma, breast cancer, colon cancer, prostate cancer, mesothelioma) cancers.


The NDC80 CAR is designed to be effective against multiple liquid and solid tumors. The CAR recognizes NDC80 peptide presented by HLA-A*02:01 which is among the most frequently presented HLA alleles in the US (~40% of the population; Pearlman et al., 2021). The NDC80 peptide has also been found on other A*02 suballeles (ex: A*02:02, :03, :04, :07, :11) which could expand the total addressable market.


Klatt et al., A TCR mimic CAR T cell specific for NDC80 is broadly reactive with solid tumors and hematologic malignancies. Blood. 2022 (link)




PCT application (PCT/US2021/054123) was filed in October 2021


David A. Scheinberg, MD, PhD, Chairman, Experimental Therapeutics Center; Vincent Astor Chair; Deputy Director, SKI, for Therapeutic Discovery


James Delorme, PhD

Licensing Manager
E-mail: [email protected]

Stage of Development

Animal studies