IPH5301 is a CD73-blocking antibody currently in Phase 1.
By targeting the adenosine immunosuppressive pathway, IPH5301 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 types of cancer. 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 the 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 degrades AMP into adenosine. The 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**.
* 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
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