title: Adoptive T-cell therapy improves treatment of canine non-Hodgkin lymphoma post chemotherapy.
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.
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: O'Connor
authors.forename: Sabina
authors.initials: S
authors.lastname: Sheppard
authors.forename: Cassie A
authors.initials: CA
authors.lastname: Hartline
authors.forename: Helen
authors.initials: H
authors.lastname: Huls
authors.forename: Mark
authors.initials: M
authors.lastname: Johnson
authors.forename: Shana L
authors.initials: SL
authors.lastname: Palla
authors.forename: Sourindra
authors.initials: S
authors.lastname: Maiti
authors.forename: Wencai
authors.initials: W
authors.lastname: Ma
authors.forename: R Eric
authors.initials: RE
authors.lastname: Davis
authors.forename: Suzanne
authors.initials: S
authors.lastname: Craig
authors.forename: Dean A
authors.initials: DA
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.forename: Heather
authors.initials: H
authors.lastname: Wilson
authors.forename: Laurence J N
authors.initials: LJ
authors.lastname: Cooper
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D004283:Dog Diseases / Q000188:drug therapy / Q000628:therapy*; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage; D015870:Gene Expression; D016130:Immunophenotyping; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy / Q000662:veterinary*; D011241:Prednisone / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology*; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone