Effective tumor vaccines generated by in vitro modification of tumor cells with cytokines and bispecific monoclonal antibodies.
Antitumor immune responses are mediated primarily by T cells. Downregulation of the major histocompatibility complex (MHC) and the molecules that costimulate the immune response is associated with defective signaling by tumor cells for T-cell activation. In vitro treatment with a combination of cytokines significantly increased the expression of MHC class I and adhesion molecules on tumor cell surfaces. When tumor cells were first incubated with a bispecific monoclonal antibody that binds antigen on tumor cells to CD28 on T cells, the modified tumor cells become immunogenic and are able to stimulate naive T cells, generating tumor-specific cytotoxic T cells in vitro. Immunization with the modified tumor cells elicits an immune response mediated by CD8+ T cells. This response protected against a challenge with parental tumor cells and cured established tumors. The approach was effective in both low immunogenic and nonimmunogenic tumor model systems. Modification of tumor cells with this two-step procedure may provide a strategy for development of tumor vaccines that is effective for cancer immunotherapy.
Guo
Y J
YJ
Tumor Immunology & Gene Therapy Center, Shanghai Second Military Medical University, People's Republic of China.
Che
X Y
XY
Shen
F
F
Xie
T P
TP
Ma
J
J
Wang
X N
XN
Wu
S G
SG
Anthony
D D
DD
Wu
M C
MC
D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000517:prevention & control*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014611:Vaccination
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D016207:Cytokines; D015395:Histocompatibility Antigens Class I