Successful treatment of melanoma brain metastases with adoptive cell therapy.
OBJECTIVE
To determine the objective response rate and response duration of melanoma brain metastases to adoptive cell therapy (ACT) with autologous antitumor lymphocytes plus interleukin-2 following a lymphodepleting preparative regimen.


METHODS
Between 2000 and 2009, 264 patients with metastatic melanoma received ACT, consisting of cyclophosphamide and fludarabine with or without total body irradiation, followed by the infusion of autologous tumor-infiltrating lymphocytes (TIL) or autologous peripheral blood lymphocytes retrovirally transduced to express a T-cell receptor (TCR) that recognized the melanocyte differentiation antigens gp-100 or MART-1. From this group, 26 patients were retrospectively identified to have had untreated brain metastases and extracranial disease before receiving ACT. The response rate and duration of melanoma brain metastases, as well as the overall response rate, response duration, and survival for these patients, are presented.


RESULTS
Seventeen of these 26 patients received ACT with TIL. Seven of these patients (41%) achieved a complete response in the brain, and six patients achieved an overall partial response. In the nine patients that received TCR-transduced lymphocytes, two patients achieved a complete response in the brain (22%) and one of these two achieved an overall partial response. One patient developed a tumor-associated subarachnoid hemorrhage during the thrombocytopenic phase of therapy and had an uneventful metastatectomy.


CONCLUSIONS
ACT with a nonmyeloablative preparative regimen using either TIL- or TCR gene-transduced cells and interleukin-2 can mediate complete and durable regression of melanoma brain metastases. This strategy can be used safely in selected patients with metastatic melanoma to the brain.
Hong
Jenny J
JJ
National Cancer Institute, Surgery Branch and The Clinical Center of the NIH, Radiology and Imaging Sciences, Bethesda, Maryland, USA.
Rosenberg
Steven A
SA
Dudley
Mark E
ME
Yang
James C
JC
White
Donald E
DE
Butman
John A
JA
Sherry
Richard M
RM
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000175:diagnosis / Q000556:secondary* / Q000628:therapy*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D012189:Retrospective Studies; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D007376:Interleukin-2