PDE Inhibitors in Immunotherapy

Defects in the immune system of tumor-bearing hosts can dramatically preclude effective immune-therapy. JHU researchers and others have previously described some of the cellular and molecular mechanisms responsible for these defects and have shown that the inhibition of these pathways can facilitate immune-mediated eradication of cancer. Specifically, immune dysfunction found in tumor-bearing animals as well as in cancer patients may be associated with the recruitment by the tumor of myeloid suppressors cells (MSCs). In a murine model of transplantable colon carcinoma, JHU Researchers demonstrated that PDE inhibition is able to delay tumor progression via an immune-mediated mechanism, namely functional and phenotypic changes in the MSC population. MSCs significantly lost their suppressive activity leading to CD8 infiltration within the tumor microenvironment; the appearance of the CD8 cells seems to be coincident with tumor regression. These data suggest that PDE inhibitors re-establish a favorable environment for effective immunotherapy. Moreover, it is possible that there is a direct anti-tumor effect as shown by the ability to induce apoptosis in immortalized human tumor lines but not in normal B-cells or activated lymphocytes. Description (Set) Proposed Use (Set) PDE inhibitors will likely serve as an adjuvant in tumor immunotherapy to abrogate the immunosuppressive effects of the tumor microenvironment. A likely synergy could be its integration with vaccines in an effort to augment anti-tumor immune responses. Moreover the translation of PDE inhibitors into the clinic for the treatment of malignancies should not be difficult, since the same compounds are already used in human for other disorders (e.g. erectile dysfunction).

Inventor(s): Borrello, Ivan

Type of Offer: Licensing

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