Patient Derived Xenograft (PDX) Model in Humanized NOG Mice: Evaluation and Validation of Immuno-oncology Agents

DESCRIPTION provided by applicant One of the most promising approaches in immunotherapy is activating antitumor immunity in patients by andapos checkpoint blockadeandapos referring to the use of antibodies that block immuno inhibitory pathways switched on by cancer cells A growing number of cancers that respond to these checkpoint blockades have now been described in patients Antibodies that block CTLA ipilimumab and PD pembrolizumab have been approved to treat patients with melanoma renal cell carcinoma and non small cell lung carcinoma with durable clinical responses However as checkpoint blockade becomes a promising therapeutic avenue for cancer therapy current preclinical models are not able to recapitulate the antitumor immune responses mediated by checkpoint blockade therapies This is partly because of the inherent differences between the mouse and the human immune systems HuMurine Technologies was founded in as a CRO to standardize and optimize the construction of andapos humanizedandapos mice Hu M tm platform stably engrafted with a human immune system The Hu M tm platform has been successfully implemented for evaluating therapies that specifically target the human immune system in a wide range of diseases models In order to address the high unmet need for a robust preclinical platform for testing the efficacy and safety of novel immunotherapies HuMurine has partnered with Championsandapos Oncology to develop and validate the PDX Hu M tm platform using the approved immune checkpoint modulators Ipilimumab and Pembrolizumab This development process will also included consultation with potential end users of the platform including major pharmaceutical companies and biotechandapos s which demonstrates a strong commercialization plan for the platform post validation This proposal aims to address a part of andquot NCIandapos s provocative questions initiativeandquot about the development of appropriate model systems to understand the human immune responses within the tumor microenvironment Validated of this novel PDX Hu M tm platform would significantly reduce the high attrition rates of immunotherapeutics in clinical trials The Specific Aims of this proposal are Aim Determine if Ipilimumab treated HLA A matched melanoma PDX Hu M tm mice generates a tumor specific T cell response Aim Determine antitumor efficacy of combinational checkpoint blockade of CTLA and PD in HLA A matched melanoma and NSCLC PDX Hu M tm mice PUBLIC HEALTH RELEVANCE Patient Derived Xenograft PDX in Humanized NOG Mice Evaluation and Validation of Immuno oncology Agents Targeting immune checkpoints using monoclonal antibodies are a novel and highly effective strategy to combat a variety of cancers by activating the antitumor immune response andquot Humanizedandquot Hu MTM mice stably engrafted with a human immune system will be engrafted with patient derived xenotransplant PDX melanoma and non small cell lung carcinoma NSCLC representing tumors that are derived from patients without being passaged in culture Ipilimumab and Pembrolizumab two clinically approved immunotherapies will be tested in this novel mouse model PDX Hu M tm to establish whether this platform can be used to screen the anticancer effects and preclinical safety of new and upcoming immune checkpoint therapies