Immunity to tumors relies on recirculating antigen-specific T cells. Whilst
induction of antigen-specific T cells by immunotherapy has been convincing
ly proven, direct evidence for recirculation of such cells is still lacking
. Here, employing a recently established in situ immunotherapy model for mu
rine melanoma we directly demonstrate the redistribution of clonally expand
ed T cells. In this model IL-2 is targeted to the tumor microenvironment by
means of specific antibody-IL-2 fusion proteins resulting in the expansion
of T cells. The therapeutic effect of the fusion protein is not restricted
to tumors expressing the targeted antigen, but extends to antigen negative
variants of the tumor if present in the same animal. Analysis of the T cel
l infiltrate by quantitative reverse transcription-PCR revealed the presenc
e of highly expressed TCR BV regions in both tumor variants. TCR clonotype
mapping revealed that the high expressions of these regions were caused by
clonal expansions and, notably, that these specific clonotypic TCR transcri
pts were identical in both tumors. Thus, T cell clones activated locally by
targeted IL-2 therapy recirculate and mediate eradication of distant tumor
sites not subjected to in situ cytokine therapy.