UCLA researchers in the Departments of Neurosurgery and Pharmacology have developed a novel platform for the identification of alternative splice variants unique to cancer cells, for use as neo-epitope vaccines or as T cell Receptor-based cell therapy of brain cancer.
BACKGROUND:
T cells are a type of lymphocyte that play a central role in immune response to antigens. T cell Receptors (TCRs), situated on the surface of T cells, are crucial for antigen recognition, and elicit an essential immune response to fight cancer. When tumor-specific proteins are fragmented into peptides, the major histocompatibility complex presents these peptide antigens to TCRs. Therefore, knowledge of alternative mRNA splice variation in tumor cells may be useful for the development of immunotherapies that recognize tumor-specific neoantigens presented to the major histocompatibility complex. No current technology is able to accurately predict and recognize splice variations unique to tumors.
INNOVATION:
UCLA researchers have created a platform for the screening and identification of alternative mRNA splice variants unique to brain cancer. Tumor infiltrating lymphocytes were demonstrated to recognize the predicted splice variant peptides. These splice variants may be presented as neoantigens complexed with the major histocompatibility complex. Neo-epitopes, from sequencing of identified alternative mRNA splice variants, can be used as a vaccine as part of a Dendritic Cell based treatment. Further, the most abundant TCR clonotypes have been sequenced and can be used as a novel TCR-based cell therapy to recognize tumor-specific protein fragments in brain cancer. This invention represents a major step forward in strategies of immunotherapy.
APPLICATIONS:
• Identification of tumor-specific splice variant neoantigens in brain cancer cells
• Neo-epitope peptide vaccines for the treatment of cancer
• T cell Receptor-based cell therapy for brain cancer
ADVANTAGES:
• Identification of alternative mRNA splice variants unique to cancer cells
• Directed immunotherapy to tumors without adverse off-target effects
• Sequenced neo-epitope peptides have the potential to be used as vaccines for a Dendritic Cell based treatment
STATE OF DEVELOPMENT:
This platform has been developed and applied to two of the most common HLA types in patients with brain cancer. These results show that T cells of cancer patients are able to recognize the predicted alternative splice variant peptides.