Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes

Author:

Dudley Mark E.1,Wunderlich John R.1,Robbins Paul F.1,Yang James C.1,Hwu Patrick1,Schwartzentruber Douglas J.1,Topalian Suzanne L.1,Sherry Richard1,Restifo Nicholas P.1,Hubicki Amy M.1,Robinson Michael R.2,Raffeld Mark3,Duray Paul3,Seipp Claudia A.1,Rogers-Freezer Linda1,Morton Kathleen E.1,Mavroukakis Sharon A.1,White Donald E.1,Rosenberg Steven A.1

Affiliation:

1. Surgery Branch, National Cancer Institute;

2. National Eye Institute;

3. Laboratory of Pathology, National Cancer Institute; National Institutes of Health, Bethesda, MD 20902, USA.

Abstract

We report here the adoptive transfer, to patients with metastatic melanoma, of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen. This approach resulted in the persistent clonal repopulation of T cells in those cancer patients, with the transferred cells proliferating in vivo, displaying functional activity, and trafficking to tumor sites. This led to regression of the patients' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction. This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus–related acquired immunodeficiency syndrome and other infectious diseases.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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