B cell tumor vaccine enhanced by covalent attachment of immunoglobulin to surface proteins on dendritic cells.
Protein antigens have been covalently linked randomly to surface proteins on immature dendritic cells (DC). This has been achieved under physiological conditions using a heterobifunctional reagent that couples antigens to free thiol groups expressed on DC surface proteins. This results in a significant increase in the amount of antigen that is bound to DC, and the antigen/membrane protein complexes that are formed are rapidly internalized. DC, loaded covalently with either beta-galactosidase (beta-gal) or a tumor-associated immunoglobulin (Ig) when injected into mice, induce a beta-gal- or Ig-specific T cell response, and a protective anti-tumor immunity for tumors expressing either beta-gal or the targeted Ig. This response is shown here to be significantly greater than that which is induced by DC that are loaded with these antigens via the conventional antigen pulse protocol. These results establish a novel, safe, and viable approach of enhancing the effectiveness of DC-based vaccination strategies for B cell lymphoma.
Lou
Qiang
Q
Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, NY 14214, USA.
Conway
Thomas F
TF
Egilmez
Nejat K
NK
Loyall
Jenni L
JL
Bernstein
Steven H
SH
Kelleher
Raymond J
RJ
Bankert
Richard B
RB
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology* / Q000628:therapy; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology* / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007136:Immunoglobulins / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D015996:Survival Rate; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D008562:Membrane Glycoproteins