Rational Design of Chimeric Antigen Receptors for Cancer Immunotherapy

Adoptive transfer of chimeric antigen receptor (CAR) T cells is a form of immunotherapy where a patient's T cells are extracted, in vitro altered to express an antigen-specific receptor coupled to an intracellular effector function activator, and adoptively transferred back into the patient to kill, for example, tumor cells expressing the targeted antigen. It is the objective of this project to design a robust bi-specific CAR, which contains a repressor element as well as an activator (the current bi-specific CARs contain only activator elements). This new CAR design will allow for targeting of cells with specific expression and non-expression, which will greatly increase the sensitivity and specificity of CAR T cells and thus increase the efficacy and clinical safety. This vastly increases the complexity of target selection. To facilitate target selection and CAR design, it is the aims of this project to utilize proteogenomic data from cancer cells and healthy cells to map the surface proteome and select robustly expressed tumor antigens. Data for this analysis will be collected by 1) proteomics analyses at OX, 2) collection from public data resources and 3) text mining the primary literature. The collected data will be published as a freely available data resource for future research projects. Following this step, I will develop analysis tools to select highly specific targets, and lastly facilitate the genetic design of CARs using software-supported cloning strategies. proteogenomic data from cancer cells and healthy cells to map the surface proteome and select robustly expressed tumor antigens. Data for this analysis will be collected by 1) proteomics analyses at OX, 2) collection from public data resources and 3) text mining the primary literature. The collected data will be published as a freely available data resource for future research projects. Following this step, I will develop analysis tools to select highly specific targets, and lastly facilitate the genetic design of CARs using software-supported cloning strategies.