Targeting of lymphotoxin-alpha to the tumor elicits an efficient immune response associated with induction of peripheral lymphoid-like tissue

A recombinant antibody-lymphotoxin-alpha fusion protein induced an adaptive immune response protecting mice from melanoma. Importantly, this fusion pr otein elicited the formation of a lymphoid-like tissue in the tumor microen vironment containing L-selectin(+) T cells and MHC class II+ antigen-presen ting cells, as well as B and T cell aggregates. Furthermore, PNAd(+)/TCA4() high endothelial venules were observed within the tumor, suggesting entry channels for naive T cell infiltrates. Over the course of therapy, a marke d clonal expansion of certain TCR specificities occurred among tumor-infilt rating lymphocytes that displayed reactivity against melanoma cells and the TRP-2(180-188) peptide. Consequently, naive T cells may have been recruite d to as well as primed and expanded in the lymphoid-like tissue induced by the lymphotoxin-alpha fusion protein at the tumor site.