Development of GIFT4: a B cell focused immunotherapy for cancer

Project Summary Our goal is to develop a novel immunotherapy for the treatment of melanomaand potentially a wide array of tumorsAlthough surveillance by the immune system eliminates cancer cells in some instancestumor cells have developed a variety of mechanisms to escape immune recognition often resulting in tumor outgrowthImmune checkpoint inhibitorse gipilimumabnivolumaband pembrolizumaband cellular immunotherapiese gadoptive cell transfer and CARchimeric antigen receptorT cellsare showing dramatic efficacy in ongoing clinical trialsHowevereven the most promising therapies are effective for a limited range of cancers and only for a minority of patientse gresponse rates with PDinhibitors areMoreoverthey can be associated with significant toxicitiesand tumorsespecially solid tumorseventually develop resistanceThe potential of B cells as anti tumor immunotherapeutics hasto a large extentremained untappedNeverthelessB cells constitute part of the cancer infiltrating immune cells and they have anti tumor properties including production of tumor suppressive cytokines and enhancing tumor killing T cell responseIndeedthe presence of B cells in the tumor microenvironment is correlated with long term survival for cancer patientsThis application is focused on advancing our preclinical development in preparation for a subsequent Investigational New DrugINDapplication to the FDAWe will determine the optimal efficacious dose of GIFTin murine models of cancerassemble a toxicology package in appropriate models and optimize exprssion and develop fermentation and large scale purification protocolsSuccessful commercialization would ultimately provide profound anti tumor immunotherapeutic benefits in a wide variety of cancer indicationsparticularly those characterized by a weakened immune system that do not respond to other immunotherapies