CAR T cells targeting STEAP1 for solid cancer therapy
Purpose: Our research group is developing chimeric antigen receptor (CAR) T cell immunotherapy targeting solid tumors. The purpose of the current application is to optimize CAR T cells delivery conditions in treating solid tumor growth in a preclinical xenograft mouse model, and to investigate the therapeutic efficacy of CAR T cells targeting the six-transmembrane antigen of the prostate (STEAP) 1 in vivo. We will also test the effect of entocytosis inhibitor, Prochlorperazine, on the CAR T cell therapy efficy.
Our CAR T cell showed significant therapeutic effect on subcutaneous mice model. To further investigate the effect of our CAR T cells on metastasis solid tumor, the common used models are inject the tumor cells either intraperitoneally or intravenously. Here we are applying to change/add the tumor injection method to intraperitoneally and intravenously.
Expected injury: Subcutaneous tumors cause minimal discomfort. Generally, T-cell therapy causes transient and reversible weight-loss.
Benefit: Experiments will facilitate optimization of T-cell immunotherapy and determine the efficacy of targeting STEAP1 in treating growth of solid tumors. If successful, these experiments provide the basis for future clinical applications.
Experiment size: The experiment setup involves the use of a total of 1422 NOD scid gamma (NSG) mice.
3R compliance: In vitro experiments have already been performed with great success. To investigate whether the results obtained in vitro are applicable to an in vivo setting, experiments in live animals are necessary. The number of mice is as low as possible, yet high enough so that it is possible to find significant differences. 10 or 12 animals per treatment group in each experiment should give sufficient data to obtain statistical significance of the results based on our and other researchers previous experience in similar experiments. Smaller groups of animals may likely not give enough statistical power. The actual number of mice used per group will be minimized, depending on initial results. If we observe any severe symptoms of reduced well-being or health of the
Our CAR T cell showed significant therapeutic effect on subcutaneous mice model. To further investigate the effect of our CAR T cells on metastasis solid tumor, the common used models are inject the tumor cells either intraperitoneally or intravenously. Here we are applying to change/add the tumor injection method to intraperitoneally and intravenously.
Expected injury: Subcutaneous tumors cause minimal discomfort. Generally, T-cell therapy causes transient and reversible weight-loss.
Benefit: Experiments will facilitate optimization of T-cell immunotherapy and determine the efficacy of targeting STEAP1 in treating growth of solid tumors. If successful, these experiments provide the basis for future clinical applications.
Experiment size: The experiment setup involves the use of a total of 1422 NOD scid gamma (NSG) mice.
3R compliance: In vitro experiments have already been performed with great success. To investigate whether the results obtained in vitro are applicable to an in vivo setting, experiments in live animals are necessary. The number of mice is as low as possible, yet high enough so that it is possible to find significant differences. 10 or 12 animals per treatment group in each experiment should give sufficient data to obtain statistical significance of the results based on our and other researchers previous experience in similar experiments. Smaller groups of animals may likely not give enough statistical power. The actual number of mice used per group will be minimized, depending on initial results. If we observe any severe symptoms of reduced well-being or health of the