Augmenting Chimeric Antigen Receptor T Cell Induced Epitope Spreading for Pediatric Solid Tumors
An increasingly promising cancer treatment involves reprogramming a patient's immune cells to recognize and destroy their tumor, called cellular immunotherapy. This exciting new discovery has been successful in eradicating certain types of pediatric blood cancers that are resistant to conventional treatments. Great effort has been made to apply cellular immunotherapy to other non-blood pediatric cancers, called solid tumors, which can involve bones, organs and other tissues. Unfortunately, we have not been successful yet at creating cellular immunotherapies that destroy solid tumors for several reasons. One major reason is that reprogrammed immune cells are designed to recognize a single marker on a cancer cell. In some blood cancers, all of the tumor cells express the same marker increasing the likelihood that cellular immunotherapy will cure a patient. Solid cancers are more heterogeneous than blood cancers, meaning each solid tumor cell may express a different marker, thus cellular immunotherapy is less likely to destroy all of tumor cells and the chance of achieving a cure is much more difficult. As a potential solution, we have demonstrated that cellular immunotherapy can induce some non-targeted cancer cells to die, triggering the immune system to react against cells that express different markers in a process called 'epitope spreading'. Unfortunately, at baseline this effect appears to be small.
The focus of this project will be to test strategies to augment epitope spreading induced by reprogrammed immune cells in pediatric solid tumors, so that cellular immunotherapy may become a viable treatment option.