Antitumor activity of dual-specific T cells and influenza virus.
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.
Murphy
A
A
Cancer Immunology Research Program, Peter MacCallum Cancer Centre, Melbourne, Australia.
Westwood
J A
JA
Brown
L E
LE
Teng
M W L
MW
Moeller
M
M
Xu
Y
Y
Smyth
M J
MJ
Hwu
P
P
Darcy
P K
PK
Kershaw
M H
MH
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*
D000951:Antigens, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases