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Sci Rep. 2012;2:249. doi: 10.1038/srep00249. Epub 2012 Feb 13.

Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy.

Author information

1
Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Abstract

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.

PMID:
22355761
PMCID:
PMC3278154
DOI:
10.1038/srep00249
[Indexed for MEDLINE]
Free PMC Article

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