02315-A: Discovering Peptide Targets for Development of Adoptive Cell Therapy for Peripheral T-Cell Lymphoma
Grant Status: Closed
T cells (a type of white blood cell known as a lymphocyte) constitute the immune system's most potent weapons against cancer, but growing malignant cells can quickly outpace and overwhelm these defenses. In the most advanced form of cancer immunotherapy, these T cells can be isolated from the body, reinvigorated and expanded to vast numbers in the test tube, and then given back to patients -- in some cases, leading to years-long remissions of advanced cancers, usually melanomas, resistant to all other treatments. While there is tremendous enthusiasm to extend this approach to lymphoma and other incurable malignancies, this has proved difficult. Sometimes T cells also recognize and attack normal tissues, causing patient death. Further, because the therapy involves living cells, and is personalized -- T cells typically target a marker unique to a specific patient's tumor -- the complexity and cost is enormous. Efforts to make this immunotherapy safer and readily available are being intensively pursued, focused on finding cancer proteins recognized by T cells that are 1) shared between patients with the same cancer, and 2) not expressed by normal tissues, sparing them from inappropriate attack. The investigators recently discovered a protein expressed by lymphoma cells across multiple canine patients; importantly, normal tissue expression appears minimal. This study's goal is to identify the correct tiny fragment (peptide) of this protein that T cells directly recognize, which then will be used to extract these T cells from patients for development of immunotherapy for dogs.
Nemec, P. S., Kapatos, A., Holmes, J. C., & Hess, P. R. (2018). The prevalent Boxer MHC class Ia allotype dog leukocyte antigen (DLA)-88*034:01 preferentially binds nonamer peptides with a defined motif. HLA, 92(6), 403–407. https://doi.org/10.1111/tan.13398
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