Mouse-derived tumor homografts, or homografts, are the "mouse version" of patient-derived xenografts (PDXs), which combine the genetic and pathol. similarities of spontaneous primary murine tumors from autochthonous models with the relative ease of transplantation of PDX. Homografts, like PDX, are typically established using tissue fragments of primary tumors via s.c./orthotopic transplantation into immunocompetent syngeneic hosts. The primary tumor source can be any spontaneous mouse tumor, including tumors arising in genetically engineered mouse models (GEMMs), or those due to aging or chem. carcinogens induction, thus increasing repertoire of cancer types and diversity of transplanted mouse tumor models. Once established (e.g. 700-1000 mm 3 ), tumor is further expanded through sequential passaging into multiple mice and biobanked, offering numerous advantages over autochthonous tumors in operational simplicity for pharmacol. research, large cohort production, tumor growth synchronization, and higher throughput efficacy studies with short timeframes. Similar to PDXs, homografts recapitulate the original disease significantly better than syngeneic models using traditional in vitro immortalized cell lines. However, unlike PDXs, these models have complete mouse immuno-competency, enabling interactions with their intrinsic microenvironments and evaluating surrogate anti-cancer immuno-therapeutics, targeted agents as well as combination therapies. With large collections of GEMMs developed, a library of homograft for different cancer types as well as mutational features offers an efficient platform to conduct population based studies to support immunotherapy research.