MD Anderson Sarcoma SPORE - The overarching goal of The University of Texas MD Anderson Cancer Center (MD Anderson) Sarcoma SPORE is to reduce the morbidity and mortality from sarcomas through innovative translational research focused on immunologic and targeted treatments. To do this, we first address two critical needs in this arena. First, sarcomas are a complex assembly of collectively rare entities that, no different from the more prevalent carcinomas, require a multidisciplinary team-based approach in both clinical and pre-clinical research. Secondly, sarcomas have the added dimension of spanning the pediatric, adolescent-young adult, and adult populations. Thus, any translational research effort must be assembled to address this patient distribution. We bring together a multidisciplinary team of clinicians, physician scientists, statistical and computational experts, and basic and translational scientists who have substantial track records in the research and treatment of sarcomas across the age spectrum. Specifically, we propose the following: Project 2 will develop an effective systemic adoptive cellular therapy platform for chordoma patients by pursuing a clinical trial of adoptive T cells targeting a well validated immunogenic epitope of Brachyury, a well-established tumorigenic chordoma protein. Project 3 will evaluate, optimize, and refine novel antibodies, which have previously been used for cell therapies and which target proteins specifically for osteosarcoma, as antibody drug conjugates, linking them to appropriate payloads for treatment in the context of a phase 2 clinical trial. Common themes emerge from these projects, including exploration of the immune system and tumor microenvironment as targets for therapeutic activity. These projects place an emphasis on osteosarcoma, the most common tumor of bone and one where we have made virtually no treatment progress in 30+ years. All projects, working in concert with a Pathology and Tissue core of sarcoma experts, incorporate state-of-the-art molecular profiling of either patient biopsies or model organism samples. The data analyses and identification of risk stratification factors will be explored with a Biostatistics and Bioinformatics Core of experienced statisticians, bioinformaticians, and computational biologists. The team is drawn from multiple departments and divisions at MD Anderson spanning pediatrics and adult sarcoma practices and will be bolstered by an active patient advocate group, a team of expert external advisors with immense experience in sarcoma research and care and a core team of administrative expertise.
