The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for a novel monoclonal antibody (mAb), RO4, that can be used to treat mesothelin (MSLN) expressing cancers.
Mesothelin (MSLN) is a surface antigen highly expressed in many solid tumors, such as mesothelioma, ovarian, and pancreatic cancers. MSLN is present at relatively low levels in mesothelial cells of healthy individuals, making it an ideal candidate for targeted therapeutics. However, the efficacy of MSLN-targeted agents is often reduced as a portion of the protein is shed from the cell surface and binds to available anti-MSLN antibodies. This reduces therapeutic engagement at the cell surface as shed MSLN acts as a decoy within tumor microenvironments, limiting antibodies from reaching and destroying tumor cells.
Researchers at National Cancer Institute (NCI) developed a novel mAb, RO4, which specifically binds to the juxta-membrane region of MSLN to block shedding. RO4 binds to the same region of MSLN as a previously developed mAb, 15B6 (NCI Ref. #E-106-2017), but in a different conformation. This allows for increased binding affinity and specificity. CAR-T cells made with humanized RO4 demonstrated higher cytotoxicity both in vitro and in vivo compared to h15B6 CAR-Ts. Additionally, hRO4 exhibited broader binding across MSLN-positive cell types compared to h15B6, suggesting wider utility in patient populations.
Researchers at the NCI seek licensing and/or co-development research collaborations for further development of RO4 that can be used to treat MSLN-positive cancers.