Perspective

Journal of Investigative Dermatology (2008) 128, 2596–2605; doi:10.1038/jid.2008.101

Immunotherapy for Advanced Melanoma

Lei Fang1,2, Anke S Lonsdorf1,2 and Sam T Hwang1

1Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Correspondence: Dr Sam T. Hwang, Dermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, MSC 1908 NIH, Building 10/Rm12N238, Bethesda, Maryland 20892-1908, USA. E-mail: hwangs@mail.nih.gov

2These authors contributed equally to this work

Received 20 November 2007; Revised 8 February 2008; Accepted 7 March 2008.

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Abstract

Immunotherapy for melanoma has undergone significant change since the first attempts to treat patients with high dose IL-2. Herein, strategies to boost patient antitumor immunity through vaccination, treatment with agents that augment host immunity, and adoptive cell transfer will be discussed. The first two strategies have yielded only limited clinical success, but adoptive cell transfer therapy, particularly following a lymphodepleting, preconditioning regimen has resulted in objective response rates approaching 50%. For a number of reasons, lymphodepletion appears to be critical for maintenance of circulating antitumor T cells following adoptive cell transfer. Balancing antitumor efficacy, autoimmunity, and reconstitution of a functioning immune system remain challenging and potentially life-threatening issues.

Abbreviations:

ACT, adoptive cell transfer; CR, complete response; CTLA, cytotoxic T lymphocyte-associated antigen; DC, dendritic cell; OR, objective response; PR, partial response; TCR, T-cell receptor; TIL, tumor-infiltrating lymphocyte; TLR, Toll-like receptor; Tregs, regulatory T cells

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