Optimization of a novel cancer immunotherapeutic antibody for human use

ABSTRACT The goal of this application is to evaluate the cancer therapeutic feasibility of CanCureandapos s humanized first in class immunostimulatory monoclonal antibody mAb huB G the Product also names CuraB During cancer development in response to oncogenic insult or stress almost ALL human cancer cells are induced to express a SURFACE molecule MIC MHC I chain related Molecule which deems to alert and ignite the immune defense machinery to eliminate cancers However this innate power of cancer control was disabled in cancer patients because human cancer cells evolved to shed the surface MIC and release soluble MIC sMIC into the circulation sMIC is highly immune suppressive and hijacks the immune systems to allow cancers to progression We have developed a mouse mAb B G that neutralizes sMIC but does not block the interaction of tumor cell bound MIC with its immunoactivating receptor NKG D Pre clinical studies in animal models have demonstrated that B G stand alone therapy remarkably induced regression andgt of spontaneous advanced primary tumors and eliminated metastasis even in tumors that are non responsive to current immune checkpoint blockade therapy B G therapy also enhanced responses to immune checkpoint blockade therapies when used in combination Mechanistically B G therapy not only eliminates the immune suppression of sMIC but also invigorates endogenous anti tumor immune responses through novel mechanisms CanCure has humanized B G In this Phase I application we propose to evaluate the therapeutic feasibility the two huB G leading candidates with Specific Aims to evaluate whether a huB G has comparable therapeutic efficacy and stability to the parental mouse B G using our established in vitro and in vivo assays to assess the risk of unwanted ADA anti drug antibody immunogenicity of the huB G candidates using well established in vitro DC T assay Completion of these tasks is critical for CanCure to justify the milestones for Phase II product development towards commercialization The outcome will have direct impact on the survival of cancer patients The proposed study will be accomplished through a collaboration of CanCure with the Medical University of South Carolina the academic partner Project Narrative In this STTR Phase I application we propose to evaluate the therapeutic feasibility of our humanized first in class cancer immunotherapeutic antibody in partnership with the Medical University of South Carolina The proposed study is critical for justifying the milestones of the next Phase of product development The outcome will directly benefit a board type of cancer patients with advanced diseases including those who failed to respond to current available immunotherapies