Superior tumor protection induced by a cellular vaccine carrying a tumor-specific T helper epitope by genetic exchange of the class II-associated invariant chain peptide

Efficient loading of MHC class II molecules with a T helper epitope of choi ce can be achieved through genetic exchange of the MHC class II-associated invariant chain peptide (CLIP) sequence with a sequence encoding the helper peptide, We have now used this method to engineer a cellular vaccine that continuously expresses a tumor-specific helper epitope in a defined costimu latory context. We provide evidence (a) that this cellular vaccine induces peptide-specific helper T cells in vivo that are functional in protecting m ice from challenge with a highly aggressive tumor, (b) that this vaccine ca n directly prime tumor-specific helper T cells in vivo, and (c) that this c ellular vaccine is superior compared a with similar cells loaded with synth etic T helper peptide in inducing tumor protection, In conclusion, cellular vaccines for activation of antigen-specific helper T cells can be greatly improved by the introduction of invariant chain constructs containing a T h elper epitope by class II-associated invariant chain peptide exchange.