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

Abstract

A recombinant antibody-lymphotoxin-alpha fusion protein induced an adaptive immune response protecting mice from melanoma. Importantly, this fusion protein elicited the formation of a lymphoid-like tissue in the tumor microenvironment containing L-selectin+ T cells and MHC class II+ antigen-presenting 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 marked clonal expansion of certain TCR specificities occurred among tumor-infiltrating lymphocytes that displayed reactivity against melanoma cells and the TRP-2(180-188) peptide. Consequently, naive T cells may have been recruited to as well as primed and expanded in the lymphoid-like tissue induced by the lymphotoxin-alpha fusion protein at the tumor site.

• Authors: D Schrama, P thor Straten, W H Fischer, A D McLellan, E B Bröcker, R A Reisfeld, J C Becker
• Journal: Immunity (Immunity) Vol. 14 Issue 2 Pg. 111-21 (Feb 2001) ISSN: 1074-7613 [Print] United States
• PMID: 11239444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Immunotoxins
• Lymphotoxin-alpha
• Recombinant Fusion Proteins

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Endothelium, Lymphatic (immunology, pathology)
• Humans
• Immunotoxins (therapeutic use)
• Lung Neoplasms (immunology, secondary, therapy)
• Lymphocytes, Tumor-Infiltrating (immunology, pathology)
• Lymphoid Tissue (immunology, pathology)
• Lymphotoxin-alpha (therapeutic use)
• Melanoma, Experimental (immunology, pathology, therapy)
• Mice
• Mice, Inbred C57BL
• Microscopy, Electron
• Neoplasm Transplantation
• Neoplasms, Connective Tissue (immunology, pathology, therapy)
• Recombinant Fusion Proteins (therapeutic use)
• T-Lymphocytes (immunology, pathology)
• Transplantation, Isogeneic