title: Antitumor activity of dual-specific T cells and influenza virus.
abstract: Activation and expansion of T cells are important in disease resolution, but tumors do not usually satisfy these immune requirements. Therefore, we employed a novel strategy whereby dual-specific T cells were generated that could respond to both tumor and influenza virus, reasoning that immunization with influenza virus would activate and expand tumor-specific cells, and inhibit tumor growth. Dual-specific T cells were generated by gene modification of influenza virus-specific mouse T cells with a chimeric gene-encoding reactivity against the erbB2 tumor-associated antigen. Dual-specific T cells were demonstrated to respond against both tumor and influenza in vitro, and expanded in vitro in response to influenza to a much greater degree than in response to tumor cells. Following adoptive transfer and immunization of tumor-bearing mice with influenza virus, dual-specific T cells expanded greatly in numbers in the peritoneal cavity and spleen. This resulted in a significant increase in time of survival of mice. However, tumors were not eradicated, which may have been due to the observed poor penetration of tumor by T cells. This is the first demonstration that the potent immunogenic nature of an infectious agent can be utilized to directly impact on T-cell expansion and activity against tumor in vivo.
authors.affiliation: Cancer Immunology Research Program, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Murphy
authors.forename: J A
authors.initials: JA
authors.lastname: Westwood
authors.forename: L E
authors.initials: LE
authors.lastname: Brown
authors.forename: M W L
authors.initials: MW
authors.lastname: Teng
authors.forename: M
authors.initials: M
authors.lastname: Moeller
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: M J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: P
authors.initials: P
authors.lastname: Hwu
authors.forename: P K
authors.initials: PK
authors.lastname: Darcy
authors.forename: M H
authors.initials: MH
authors.lastname: Kershaw
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015674:Mammary Neoplasms, Animal / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009975:Orthomyxoviridae / Q000276:immunology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*
chemical_list: D000951:Antigens, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases