Lymphotoxin-β, lymphotoxin-β complexes, pharmaceutical preparations and therapeutic uses thereof
View Patent ↗This invention relates to lymphotoxin-β, a lymphocyte membrane type protein. This protein is found on the surface of a number of cells, including phorbol ester (PMA) stimulated T cell hybridoma II-23.D7 cells. This invention also relates to complexes formed between lymphotoxin-β and other peptides such as lymphotoxin-α and to complexes comprising multiple subunits of lymphotoxin-β. These proteins and complexes are useful in holding LT-α formed within the cell on the cell surface where the LT-α/LT-β complex may act as an inflammation regulating agent, a tumor growth inhibiting agent, a T cell inhibiting agent, a T cell activating agent, an autoimmune disease regulating agent, or an HIV inhibiting agent. Furthermore, the antitumor activity of the LT-α/LT-β complex may be delivered to tumor cells by tumor infiltrating lymphocytes (TILs) transfected with the gene for LT-β.
1. A method for treating or lessening the advancement, severity, or effects of neoplasia, comprising administering an effective amount of a composition comprising a pharmaceutically acceptable carrier and a polypeptide complex comprising a first polypeptide selected from a group consisting of
(a) a polypeptide comprising the amino acid sequence defined by SEQ ID NO: 2;
(b) a polypeptide comprising the amino acid sequence defined by SEQ ID NO: 4;
(c) a polypeptide comprising the amino acid sequence defined by SEQ ID NO: 6;
(d) a polypeptide comprising the amino acid sequence defined by SEQ ID NO: 2 wherein the amino acids Leu Gly Leu at the amino terminus of said sequence are replaced by a single Met or Leu residue; and
a second polypeptide which is lymphotoxin-α.
2. The method of claim 1 , wherein the first polypeptide is a polypeptide comprising the amino acid sequence defined by SEQ ID NO: 2.
3. The method of claim 1 , wherein the first polypeptide is a polypeptide comprising the amino acid sequence defined by SEQ ID NO: 4.
4. The method of claim 1 , wherein the first polypeptide is a polypeptide comprising the amino acid sequence defined by SEQ ID NO: 6.
5. The method of claim 1 , wherein the first polypeptide is a polypeptide comprising the amino acid sequence defined by SEQ ID NO: 2, wherein the amino acids Leu Gly Leu at the aimno terminus of said sequence are replaced by a single Met or Leu residue.