Home  |  About the Book  |  Table of Contents  |  Search  |  Archive  |  Order  |  Visit JCO  |  Visit ASCO.org
ASCO Educational Book; 2009
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar content in this book
Right arrow Download to citation manager
Right arrowRights & Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dudley, M. E.
Right arrow Articles by Rosenberg, S. A.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Dudley, M. E.
Right arrow Articles by Rosenberg, S. A.

Clinical Trials Investigating Adoptive Cell Therapy Combined with Lymphodepletion for Patients with Advanced Cancer

Mark E. Dudley, PhD, and Steven A. Rosenberg, MD, PhD

From the Tumor Immunology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

Address reprint requests to Steven A. Rosenberg, MD, PhD, Head of the Tumor Immunology Section, Branch Chief, Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10-CRC, Room 3-3940, 10 Center Drive, MSC 1201, Bethesda, MD 20892; e-mail: sar{at}nih.gov

Overview: For patients with melanoma, tumor-reactive lymphocytes can often be identified from melanoma biopsies, and these tumor-infiltrating lymphocytes (TILs) can be activated and numerically expanded. Initial studies with TILs administered to autologous patients, along with interleukin-2 therapy, demonstrated that TILs could mediate tumor regressions, but the clinical responses were generally short in duration and persistence of the transferred T cells was minimal. Studies in mouse models suggested that prior lymphodepletion could enhance adoptive cell therapy (ACT) and motivated the initiation of clinical trials combining lymphodepletion with ACT for the treatment of patients with refractory melanoma. ACT with tumor-reactive TILs in lymphodepleted patients in three sequential clinical trials resulted in objective responses in 52 of 93 patients (56%), including 13 complete responders. Some patients exhibited the persistence of high levels of transferred, tumor-reactive lymphocytes in their peripheral blood. The adverse effects of this treatment included transient marrow suppression caused by chemotherapy and the known consequences of interleukin-2 therapy. In these sequential trials, there was a trend toward better survival in patients who received increased intensity ablative regimens. Additional improvements could include simplification of the lymphocyte culture process, use of minimally cultured TILs that may persist longer in vivo, or genetically retargeted lymphocytes that recognize a wider array of cancer antigens; and by coadministration of lymphocyte-activating agents. ACT with lymphodepletion is a safe and potentially curative treatment for many patients with refractory melanoma.