Immune response enhancement by in vivo administration of B7.2Ig, a soluble costimulatory protein.
The identification of both class I- and class II-restricted tumor-associated peptides recognized by T cells has led to the test of these peptides as immunogens in experimental immunotherapy for cancer patients. However, optimal T cell activation requires signaling both through the T cell receptor for antigen and through costimulatory pathways. B7.1 and B7.2 are powerful costimulatory molecules expressed on the surface of antigen-presenting cells. Using a mouse model, we have sought to optimize costimulatory signals during antipeptide responses by administering a soluble form of B7.2 at the time of peptide immunization. Administration of B7. 2Ig fusion protein significantly enhanced T helper cell and CTL responses. These findings suggest that soluble forms of human B7.2 protein may provide a straightforward and practical method of supplying optimal costimulation during clinical immunotherapy.
Swiniarski
H
H
Genetics Institute, One Burtt Road, Andover, Massachusetts, 01810, USA.
Sturmhoefel
K
K
Lee
K
K
Gray
G S
GS
Thomas
J L
JL
Wolf
S F
SF
Dorner
A J
AJ
O'Toole
M
M
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D015703:Antigens, CD / Q000494:pharmacology*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D007136:Immunoglobulins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000502:physiology; D018793:Interleukin-13 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012995:Solubility; D013601:T-Lymphocytes / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D018793:Interleukin-13; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D007371:Interferon-gamma