Neoantigens resulting from the inherent genomic instability of tumor cells
generally do not trigger immune recognition. Similarly, transfection of tum
ors with model Ags often fails to elicit CD8(+) T cell responses or alter a
tumor's growth rate or lethality. We report here that the adoptive transfe
r of activated Th1-type CD4(+) T cells specific for a model tumor Ag result
s in the de novo generation of CD8(+) T cells with specificity to that Ag a
nd concomitant tumor destruction. The anti-tumor effects of the CD4(+) T ce
lls required the presence of both MHC class I and class II on host cells, a
s evidenced by experiments in knockout mice, suggesting that CD4(+) T cells
enhanced the ability of host APC to activate endogenous CD8(+) T cells. Th
ese results indicate that the apparent inability of tumor cells expressing
highly immunogenic epitopes to activate tumor-specific CD8(+) T cells can b
e altered by activated CD4(+) T cells.