About this program
This program aims at developing an anti-CD73 antibody for immuno-oncology. By targeting the adenosine immunosuppressive pathway, it has the potential to promote anti-tumor immune responses across a wide range of tumors.
CD73 is a membrane-bound extracellular enzyme overexpressed in several cancer types. Its expression has been linked to poor prognosis in melanoma, colorectal, gastric, triple negative breast cancer, and to a pro-metastatic phenotype in prostate cancer*.
Together with CD39, it plays a major role in promoting immunosuppression through the pathway degrading adenosine triphosphate (ATP) into adenosine. Within the tumor microenvironment, ATP promotes immune cell-mediated killing of cancer cells. In contrast, adenosine accumulation causes immune suppression, dysregulation of immune cell infiltrates and stimulates angiogenesis resulting in tumor spreading. CD73 is active on the last step of the degradation pathway, where it is the enzyme that actually degrades AMP into adenosine. CD73-blockade promotes anti-tumor immunity by reducing adenosine accumulation. Accordingly, anti-CD73 mAbs stimulate anti-tumor immunity and reduce tumor metastasis in mouse tumor models, and could enhance the efficacy of treatment with anti-PD1 or anti-CTLA4 antibodies**.
Innate Pharma has selected the lead candidate, IPH5301, a CD-73-blocking antibody aiming at restoring a pro-inflammatory microenvironment, currently in preclinical development.
* Liu et al., 2012; Wu et al., 2012; Lu et al., 2013; Loi et al., 2013; Wang et al., 2012; Yang et al., 2013
** Allard et al., 2013
Mechanism of action of IPH5301 (anti-CD73)
Demaria, Carvelli, Batista, Thibult, A. Morel, André, Y. Morel, Vély, Vivier et al, 2020. Identification of druggable inhibitory immune checkpoints on Natural Killer cells in COVID-19 Cellular & Molecular Immunology Ivan Perrot et al, 2019. Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies Cell Reports Bastid et al, 2015. Inhibition of CD39 enzymatic function at the surface of tumor cells alleviates their immunosuppressive activity Cancer Immunol Res. Bastid et al, 2013. CD39 is a promising therapeutic target in oncology Oncogene