T-Cell Immunotherapy

T-cell lymphocytes are a type of immune white blood cells in the human body. They.are usually divided into two major subsets that are functionally and identifiably different. The T helper subset, also called the CD4+ T cell, is a pertinent coordinator of immune regulation. The main function of the T helper cell is to augment or potentiate immune responses by the secretion of specialized factors that activate other white blood cells to fight off infection.

Another important type of T cell is called cytotoxic T killer/suppressor subset (CTL) or CD8+ T cell. These cells are important in directly killing certain tumor cells, viral-infected cells and sometimes parasites. The CD8+ T cells are also important in down-regulation of immune responses.

Both types of T cells can be found throughout the body. They often depend on the secondary lymphoid organs (the lymph nodes and spleen) as sites where activation occurs, but they are also found in other tissues of the body, most conspicuously the liver, lung, blood, and intestinal and reproductive tracts.

T-Cell Immunotherapy

Cytotoxic T-lymphocytes (CTL) are also an important component of the immune system in the fight against lymphoma and other cancers. One approach to directing these immune cells to fight lymphoma cells is by gene therapy and this is an emerging technology. Genetically modified CTL can recognize lymphoma cells like a monoclonal antibody, but then attack the lymphoma cells like a “killer” T-cell.

The procedure works like this: leukocytes are gathered from the patient through apheresis. A gene is inserted so the cells express a receptor that targets lymphoma cells. The cells are multiplied many times by expansion and then reinfused into the patient where it is hoped they will kill the cancer cells and provide a level of immunity from the cancer returning.

T-cell immunotherapy is an evolving and emerging form of cancer therapy and many different research groups have been working on this in the laboratory to learn whether this could be an effective and non-toxic way of treating cancer. The Fred Hutchinson Cancer Research Center in Seattle, Washington and the City of Hope Medical Center in Duarte, California USA have been developing this technology and are working on this in the lab. They are beginning phase 1 clinical trials for follicular lymphoma, mantle cell lymphoma, and other indolent CD20+ B-Cell lymphomas (SLL/CLL, marginal zone, LPL) patients. For more information on the FHCRC/City of Hope trials call +1-206-667-5184 or go to http://www.fhcrc.org/patient/treatment/trials/details.phtml?searchTerms=473&searchFields=ProtID&searchKind=clinical.

Resources

• The Immune System - An Overview
• Gene Therapy Information for Patients and the Public - by the American Society of Gene Therapy (ASGT)

References

• Correspondence, Dr. Eric Chen, MD/PhD, Senior Fellow, Fred Hutchinson Cancer Research Center, December 2004
• William Y. Ho, Joseph N. Blattman, Michelle L. Dossett, Cassian Yee, and Philip D. Greenberg, Adoptive immunotherapy: Engineering T cell responses as biologic weapons for tumor mass destruction, Cancer Cell, Vol. 3, pp. 431-437, May 2003 PubMed
• Michel Sadelain, Isabelle Rivière and Renier Brentjens, Targeting Tumours with Genetically Enhanced T Lymphocytes, Nature, Volume 3, pp. 35-45, January 2003. PubMed
• Francesco M. Marincola, Ena Wang, Meenhard Herlyn, Barbara Seliger and Soldano Ferrone, Tumors as elusive targets of T-cell-based active immunotherapy, Trends in Immunology, Vol.24, No. 6, pp 334-341, June 2003 PubMed
• Michael C. Jensen, Patrick Clarke, Giselle Tan, Christine Wright, Wen Chung-Chang, Teresa N. Clark, Feiyu Zhang, Marilyn L. Slovak, Anna M. Wu, Stephen J. Forman, and Andrew Raubitschek, Human T Lymphocyte Genetic Modification with Naked DNA, Molecular Therapy, Vol 1, No 1, pp 49-55, Jan. 2000 PubMed
• Jinjuan Wang, Oliver W. Press, Catherine G. Lindgren, Philip Greenberg, Stanley Riddell, Xiaojun Qian, Christian Laugen, Andrew Raubitschek, Stephen J. Forman, and Michael C. Jensen, Cellular Immunotherapy for Follicular Lymphoma Using Genetically Modified CD20-Specific CD8+ Cytotoxic T Lymphocytes, Molecular Therapy, Vol. 9, No. 4, pp. 577-586, April 2004. PubMed
• Gottschalk S, Heslop H, Rooney C., Adoptive Immunotherapy for EBV-associated Malignancies, Leuk. Lymphoma 46(1): 1-10, January 2005 Pubmed