title: The combination of cyclophosphamide and human T cells genetically engineered to target CD19 can eradicate established B-cell lymphoma.
abstract: T cells genetically engineered to express tumour-targeting receptors are attractive anti-cancer therapeutic agents. Human T cells engrafted with a chimeric receptor specific for the B-cell lymphoma antigen CD19 fused to the CD3zeta receptor (aCD19z) are functional in vitro. Current successful clinical protocols targeting melanoma use pre-conditioning chemotherapy in combination with T cells. This study demonstrated that interleukin-2 expanded aCD19z T cells combined with cyclophosphamide effectively treated five-day established Raji B-cell lymphoma in an immunocompromised model system with 50% of mice surviving >100 days. This observation strongly supports the combination of antibody targeted T cells with chemotherapy as a novel approach for the therapy of CD19(+) B-cell malignancies.
authors.affiliation: Cancer Research UK Department of Medical Oncology, University of Manchester, Manchester, UK.
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Cheadle
authors.forename: David E
authors.initials: DE
authors.lastname: Gilham
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hawkins
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005818:Genetic Engineering; D005822:Genetic Vectors; D018796:Immunoconjugates / Q000008:administration & dosage*; D016393:Lymphoma, B-Cell / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes
chemical_list: D018941:Antigens, CD19; D018796:Immunoconjugates; D003520:Cyclophosphamide