Mechanism of Action

Why CD73

CD73 also known as ecto-5'-nucleotidase, or Ecto5'NTase, is a membrane-bound/free protein that can hydrolyze AMP to adenosine. Adenosine inhibits the tumor immune response through interaction with the adenosine receptors, or P1 receptors, on the cell surface. CD73 is often highly expressed and indicative of a poor prognosis in various tumor tissues, including gastric cancer, renal cell carcinoma, prostate cancer, triple negative breast cancer, and non-small cell adenocarcinoma.

 

JAB-BX102 specifically binds to CD73 and blocks its extracellular-5'-nucleotidase activity. This decreases the production of adenosine and consequently relieves the inhibitory effects of adenosine on the proliferation and tumor killing activity of CD8+ T cells. This modulation effectively enhances the anti-tumor immune response in the tumor microenvironment. Tumor immunotherapy represented by PD-(L)1 antibodies, has been widely used in clinical practice, but with its wide application, it also exposes defects such as limited response rate. Adenosine pathway activation is one of the important reasons for the low response rate of PD-(L)1 treatment. Therefore, the combination of CD73 monoclonal antibody and PD-(L)1 monoclonal antibody is expected to further improve the therapeutic effects of immune therapy.

Indications

CD73 is over-expressed in many malignant tumors, including melanoma, triple negative breast cancer, non-small cell lung cancer, renal cell carcinoma, bladder cancer, prostate cancer, gastric cancer, colorectal cancer, ovarian cancer, and malignant glioma. Preliminary clinical results of other CD73 inhibitors suggest that it has potential clinical efficacy in non-small cell lung cancer, triple negative breast cancer, renal cell carcinoma, and other solid tumors.

Clinical Trials

Asset

Programs

Region

Phase

Indication

Registration information

JAB-BX102

Monotherapy or Combo w/PD-1 mAb

Global

I

Solid tumor

ClinicalTrilas: NCT05174585

Posters & Publications  

JAB-X1800: a potent immunostimulatory antibody-drug conjugate (iADC) targeting CD73

Jacobio Pharma presented preclinical study data of JAB-X1800 at the 2023 AACR Annual Meeting

 

References

  • Turiello, R., Pinto, A., and Morello, S. (2020). CD73: A Promising Biomarker in Cancer Patients. Front Pharmacol 11, 609931.
  • Neo, S. Y., Yang, Y., Record, J., Ma, R., Chen, X., Chen, Z., Tobin, N. P., Blake, E., Seitz, C., Thomas, R., et al. (2020). CD73 immune checkpoint defines regulatory NK cells within the tumor microenvironment. J Clin Invest 130, 1185-1198.
  • Harvey, J. B., Phan, L. H., Villarreal, O. E., and Bowser, J. L. (2020). CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers. Front Immunol 11, 508.
  • Vijayan, D., Young, A., Teng, M. W. L., and Smyth, M. J. (2017). Targeting immunosuppressive adenosine in cancer. Nature reviews Cancer 17, 709-724.
  • Zhang, H., Conrad, D. M., Butler, J. J., Zhao, C., Blay, J., and Hoskin, D. W. (2004). Adenosine acts through A2 receptors to inhibit IL-2-induced tyrosine phosphorylation of STAT5 in T lymphocytes: role of cyclic adenosine 3',5'-monophosphate and phosphatases. J Immunol 173, 932-944.