Mouse B7-H3 induces antitumor immunity.
Members of the B7 family costimulate the proliferation of lymphocytes during the initiation and maintenance of antigen-specific humoral and cell-mediated immune responses. While B7-1 and -2 are restricted to lymphoid tissues, and activate naïve T cells, recently identified members including B7-H2 and -H3 are widely expressed on nonlymphoid tissues, and regulate effector lymphocytes in the periphery. B7-H3 has properties that suggested it may display antitumor activity, including the ability to stimulate Th1 and cytotoxic T-cell responses. Here, we test this notion by determining whether intratumoral injection of an expression plasmid encoding a newly described mouse homologue of B7-H3 is able to eradicate EL-4 lymphomas. Intratumoral injection of a mouse B7-H3 pcDNA3 expression plasmid led to complete regression of 50% tumors, or otherwise significantly slowed tumor growth. Mice whose tumors completely regressed resisted a challenge with parental tumor cells, indicating systemic immunity had been generated. B7-H3-mediated antitumor immunity was mediated by CD8(+) T and NK cells, with no apparent contribution from CD4(+) T cells. In summary, the results indicate that B7-H3 interactions may play a role in regulating cell-mediated immune responses against cancer, and that B7-H3 is a potential therapeutic tool.
Sun
X
X
Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Science, University of Auckland, Auckland, New Zealand.
Vale
M
M
Leung
E
E
Kanwar
J R
JR
Gupta
R
R
Krissansen
G W
GW
D000595:Amino Acid Sequence; D000818:Animals; D060887:B7 Antigens; D018122:B7-1 Antigen / Q000235:genetics*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004247:DNA / Q000008:administration & dosage*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D015552:Injections, Intralesional; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D013953:Thymus Neoplasms / Q000276:immunology / Q000628:therapy*
D060887:B7 Antigens; D018122:B7-1 Antigen; C486038:Cd276 protein, mouse; D004247:DNA