Priming protective CD8 T cell immunity by DNA vaccines encoding chimeric, stress protein-capturing tumor-associated antigen.
DNA vaccines encoding heat shock protein (hsp)-capturing, chimeric peptides containing antigenic determinants of the tumor-associated Ag (TAA) gp70 (an envelope protein of endogenous retrovirus) primed stable, specific, and tumor-protective CD8 T cell immunity. Expression of gp70 transcripts was detectable in most normal tissues but was particularly striking in some (but not all) tumor cell lines tested (including the adenocarcinoma cell line CT26). An approximately 200 residue gp70 fragment or its L(d)-binding antigenic AH1 peptide cloned in-frame behind an hsp-capturing (cT(272)) or noncapturing (T(60)) N-terminal large SV40 tumor Ag sequence was expressed as either hsp-binding or -nonbinding chimeric Ags. Only hsp-capturing, chimeric fusion proteins were expressed efficiently in transfected cell lines and primed TAA-specific CD8 T cell immunity. This immunity mediated protection in the CT26 and mKSA models. A vaccination strategy based on delivering antigenic, hsp-associated TAA fragments can thus prime protective CD8 T cell immunity even if these TAA are of low intrinsic immunogenicity.
Schirmbeck
Reinhold
R
Department of Internal Medicine I, University of Ulm, Ulm, Germany. reinhold.schirmbeck@uniklinik-ulm.de
Riedl
Petra
P
Kupferschmitt
Mark
M
Wegenka
Ursula
U
Hauser
Hansjörg
H
Rice
Jason
J
Kröger
Andrea
A
Reimann
Jörg
J
D000230:Adenocarcinoma / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016399:Lymphoma, T-Cell / Q000276:immunology / Q000517:prevention & control; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050506:Mutant Chimeric Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006023:Glycoproteins; D006360:Heat-Shock Proteins; D050506:Mutant Chimeric Proteins; D010446:Peptide Fragments; D019444:Vaccines, DNA; C033589:glycoprotein gp70, murine serum