Generation of autoreactive CTL by tumour vaccines containing foreign T helper epitopes.
The aim of this study was to evaluate the effect of including a foreign T helper cell epitope in vaccines designed for generation of CTL against self-antigens and for inhibition of tumour growth. Two different vaccine designs were composed, a minimal epitope vaccine and a modified full length self-antigen, both based on OVA containing either a colinearily synthesized or an inserted Th-epitope, respectively. These vaccines were used for immunization of tolerant OVA transgenic mice (RIP-OVA(low)) and non-tolerant C57BL/6 mice. First, it was shown that transgenic mice were tolerant to OVA in the CD4 compartment. Secondly, only the vaccines containing the foreign Th-epitope and not the wild-type constructs were able to induce self-reactive CTL in the transgenic mice. Thirdly, these self-reactive CTL induced by the Th-epitope modified constructs also inhibited tumour growth in the OVA transgenic mice. Overall, these results demonstrate that inclusion of a foreign Th-epitope circumvents the tolerance in this OVA transgenic strain. In addition, these results show the importance of including strong T-cell help in cancer vaccines.
Steinaa
L
L
Pharmexa A/S, Hørsholm, Denmark.
Rasmussen
P B
PB
Rygaard
J
J
Mouritsen
S
S
Gautam
A
A
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004527:Egg Proteins / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D001324:Autoantigens; D019496:Cancer Vaccines; D004527:Egg Proteins; D018984:Epitopes, T-Lymphocyte; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin