Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy.
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Clinical observations reveal that an augmented pace of T-cell recovery after chemotherapy correlates with improved tumor-free survival, suggesting the add-back of T cells after chemotherapy may improve outcomes. To evaluate adoptive immunotherapy treatment for B-lineage non-Hodgkin lymphoma (NHL), we expanded T cells from client-owned canines diagnosed with NHL on artificial antigen presenting cells (aAPC) in the presence of human interleukin (IL)-2 and IL-21. Graded doses of autologous T cells were infused after CHOP chemotherapy and persisted for 49 days, homed to tumor, and significantly improved survival. Serum thymidine kinase changes predicted T-cell engraftment, while anti-tumor effects correlated with neutrophil-to-lymphocyte ratios and granzyme B expression in manufactured T cells. Therefore, chemotherapy can be used to modulate infused T-cell responses to enhance anti-tumor effects. The companion canine model has translational implications for human immunotherapy which can be readily exploited since clinical-grade canine and human T cells are propagated using identical approaches.
author list (cited authors)
O'Connor, C. M., Sheppard, S., Hartline, C. A., Huls, H., Johnson, M., Palla, S. L., ... Cooper, L.
complete list of authors
O'Connor, Colleen M||Sheppard, Sabina||Hartline, Cassie A||Huls, Helen||Johnson, Mark||Palla, Shana L||Maiti, Sourindra||Ma, Wencai||Davis, R Eric||Craig, Suzanne||Lee, Dean A||Champlin, Richard||Wilson, Heather||Cooper, Laurence JN