Published on June 19, 2008 at 4:06 AM
The patient in the journal report was one of nine patients with metastatic melanoma who were being treated in a recently completed clinical trial to test dose- escalation of autologous CD4+ T cells. Earlier studies performed by Yee used CD8+ T cells, which do not persist in the body without the support of CD4+ T cells or growth factors such as interleukin 2. Yee and colleagues theorized that infusion of a massive dose of CD4+ T cells would persist longer in the body because they make their own growth factor, interleukin 2, while stimulating the anti-tumor effect of the patient's existing CD8+ T cells. However, until recently there was no feasible way to isolate and expand anti-tumor CD4+ T cells in the lab.
The researchers were successful in all of these areas. The patient received a dose of 5 billion cloned CD4+ T cells with specificity for the melanoma-associated NY-ESO-1 antigen. The cells persisted for at least 80 days in the patient's body. And, even though only 50 percent to 75 percent of the patient's tumor cells expressed the NY-ESO-1 antigen, the entire tumor regressed following the infusion. The scientists postulated that the patient's immune response was broadened to other antigens expressed by the tumor cells. Follow-up tests showed T-cell responses to two additional tumor antigens, MAGE-3 and MART-1.
Researchers in Yee's lab, the University of Washington School of Medicine and the Ludwig Institute for Cancer Research in New York collaborated on the research. The Burroughs-Wellcome Foundation, Damon Runyon Cancer Research Foundation, Edson Foundation and National Cancer Institute funded the study.