20107 Background: More than 2000 tumor antigens have been identified so far. However, none of these tumor antigens are approved to be immunogenic. Genetic alteration which activates uncontrolled cell growth transforms normal cells to tumor cells. Tumor cells, therefore, do not carry any foreign antigens and thus tumor antigens are not immunogenic (unless in the presence of viral infection). The so-called tumor specific immunity is actually the host versus graft effect, not specific for tumors. Methods and Results: Using proper controlled tissue graft as control, our previous data indicated that the hosts could accept both the graft and the tumor. The immune system is silent to tumor antigens. By transfecting tumor cells with a modified LIGHT (Lymphotoxins, shows Inducible expression, and completes with herpes simplex virus Glycoprotein D for Herpes virus entry mediator, a receptor expressed by T lymphocytes) expressing vectors, Dr. Fu at the University of Chicago is able to eradicate tumors in his animal model. The expressed LIGHT on the tumor cell surface serves as tether for the naïve T cells and the stromal cells by binding to lymphotoxin-beta receptor on stromal cells and herpes virus entry mediator on T cells. The trio of tumor-LIGHT-stroma working like a foreign antigen attracts naïve T cells and increases the infiltration of naïve T cells within the tumors. The trio then co-activates naïve T cells to destroy tumors. The LIGHT mechanism may be similar to that in autoimmune phenomenon. Conclusion: Tumor specific immunity may be silent; however we can modify tumor antigens and activate silent immune system to destroy tumors. We currently have four immunotherapies against cancer. The LIGHT approach or in situ co-stimulation therapy, vaccine therapy, and ex vivo cell-transfer therapy are three active immunotherapies. The fourth one is a passive immunotherapy: the near-specific, personalized immunotherapy. No significant financial relationships to disclose.
Age is not just a number: Naive T cells increase their ability to persist in the circulation over time