Antitumor response elicited by a superantigen-transmembrane sequence fusion protein anchored onto tumor cells.

Abstract

Superantigens stimulate T cells bearing certain TCR beta-chain variable regions when bound to MHC II molecules. We investigated whether the superantigen toxic shock syndrome toxin-1 (TSST1) could induce an antitumor immune response when anchored onto MHC II-negative tumor cells. Our approach was to facilitate association of TSST1 with cell membranes by fusing its coding region to the transmembrane region (TM) sequence of the proto-oncogene c-erb-B-2. TSST1-TM was expressed in bacteria with an N-terminal histidine tag and purified using nickel-agarose affinity chromatography. Purified TSST1-TM added to cultures of several different MHC II-negative tumor cells spontaneously associated with cell membranes, as detected by flow cytometry. Because superantigens can direct cell-mediated cytotoxicity against MHC II-positive cells, a TM fusion protein lacking the TSST1 MHC II binding domain (TSST(88-194)-TM) was also constructed. Tumor cells precoated with TSST1-TM or TSST(88-194)-TM stimulated proliferation of human peripheral blood lymphocytes in vitro whereas uncoated tumor cells did not. Mice preimmunized with TSST1-TM- or TSST(88-194)-TM-coated tumor cells mounted a systemic response that resulted in significant antitumor immunity as measured by regression of a parental tumor challenge. TSST1-TM and TSST(88-194)-TM fusion proteins represent a useful new strategy for attaching superantigens or potentially other proteins onto tumor cell surfaces without genetic manipulation.

• Authors: J L Wahlsten, C D Mills, S Ramakrishnan
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 161 Issue 12 Pg. 6761-7 (Dec 15 1998) ISSN: 0022-1767 [Print] United States
• PMID: 9862706 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, Bacterial
• Antigens, Surface
• Bacterial Toxins
• Cancer Vaccines
• Enterotoxins
• HLA-D Antigens
• MAS1 protein, human
• Membrane Proteins
• Proto-Oncogene Mas
• Recombinant Fusion Proteins
• Superantigens
• enterotoxin F, Staphylococcal
• Receptor, ErbB-2

Topics

• Animals
• Antigens, Bacterial (chemistry, genetics, immunology)
• Antigens, Surface (chemistry, immunology)
• Bacterial Toxins
• Cancer Vaccines
• Carcinoma, Lewis Lung (immunology, pathology)
• Cytotoxicity, Immunologic
• Enterotoxins (chemistry, genetics, immunology)
• Female
• HLA-D Antigens (analysis)
• Humans
• Immunization
• Lymphocyte Activation
• Lymphoma, T-Cell (immunology, pathology)
• Mast-Cell Sarcoma (immunology, pathology)
• Membrane Proteins (chemistry, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred DBA
• Neoplasm Transplantation
• Ovarian Neoplasms (immunology, pathology)
• Proto-Oncogene Mas
• Receptor, ErbB-2 (chemistry, genetics, immunology)
• Recombinant Fusion Proteins (chemistry, immunology)
• Sequence Deletion
• Staphylococcus aureus (genetics, immunology)
• Superantigens (genetics, immunology)
• Tumor Cells, Cultured