Light-mediated anti-cell proliferative compositions and methods
The tumor-necrosis factor superfamily member LIGHT (p30; TNFSF-14) is a cytokine for inducing immune responses against tumors. A novel biochemical approach is used to decorate the surface of tumor cells with LIGHT. LIGHT decorated cells can be used to vaccinate and induce effective, sustained immunity against cells expressing neo or pathogen associated antigens. Variants of LIGHT are described that enhance binding to cellular receptors (e.g., LT beta receptor) and decrease regulation by inhibitors (e.g., Decoy Receptor 3) increasing ability to stimulate immunity.
1. A method of promoting, stimulating, inducing or increasing T cell immunity against a hyperproliferative cell, tumor cell, cancer cell or metastatic cell comprising administering to a subject an amount of a cell having LTbeta receptor agonist attached, conjugated or coupled to the cell membrane effective to promote, stimulate, induce or increase the subject's T cell immunity against the hyperproliferative cell, tumor cell, cancer cell or metastatic cell wherein the LTbeta receptor agonist comprises the amino acid sequence selected from any one of SEQ ID NOs:4 to 10.
2. The method of claim 1 , wherein the LTbeta receptor agonist comprises a LIGHT (p30 polypeptide) amino acid sequence with greater affinity for LTbR or HVEM as compared to native wild type LIGHT (p30 polypeptide).
3. The method of claim 1 , wherein the LTbeta receptor agonist comprises SEQ ID NO:4.
4. The method of claim 1 , wherein the LTbeta receptor agonist comprises SEQ ID NO:5.
5. The method of claim 1 , wherein the LTbeta receptor agonist comprises SEQ ID NO:6.
6. The method of claim 1 , wherein the LTbeta receptor agonist comprises SEQ ID NO:7.
7. The method of claim 1 , wherein the LTbeta receptor agonist comprises SEQ ID NO:8.
8. The method of claim 1 , wherein the LTbeta receptor agonist comprises SEQ ID NO:9.
9. The method of claim 1 , wherein the LTbeta receptor agonist comprises SEQ ID NO:10.