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Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma
- Source :
- Proceedings of the National Academy of Sciences of the United States. July 8, 2003, Vol. 100 Issue 14, p8372, 6 p.
- Publication Year :
- 2003
-
Abstract
- Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c. vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). This blockade of CTLA-4 induced grade III/IV autoimmune manifestations in six patients (43%), including dermatitis, enterocolitis, hepatitis, and hypophysitis, and mediated objective cancer regression in three patients (21%; two complete and one partial responses). This study establishes CTLA-4 as an important molecule regulating tolerance to 'self' antigens in humans and suggests a role for CTLA-4 blockade in breaking tolerance to human cancer antigens for cancer immunotherapy.
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 100
- Issue :
- 14
- Database :
- Gale General OneFile
- Journal :
- Proceedings of the National Academy of Sciences of the United States
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.105917795