Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. 1282 5

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells and resting CD4CD25 T cells. In patients with advanced melanoma, our group reported that administration of anti-CTLA-4 antibody mediated objective cancer regression in 13% of patients. This study also established that the blockade of CTLA-4 was associated with grade III/IV autoimmune manifestations that included dermatitis, enterocolitis, hepatitis, uveitis, and a single case of hypophysitis. Since this initial report, 7 additional patients with anti-CTLA-4 antibody-induced autoimmune hypophysitis have been accumulated. The characteristics, clinical course, laboratory values, radiographic findings, and treatment of these 8 patients are the focus of this report.
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PMID:Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. 1622 77

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells and resting CD4+CD25 T cells. In patients with advanced melanoma, anti-CTLA-4 antibody therapy achieves cancer regression in 15% of patients. Treatment may be associated with grade III/IV autoimmune manifestations that included dermatitis, enterocolitis, hepatitis, uveitis, and rarely hypophysitis. Many of these toxicities require and respond to brief courses of high-dose corticosteroids. We report on a case of autoimmune hypophysitis with severe clinical symptoms that resolved rapidly after treatment with steroids. It is important to consider both autoimmune hypophysitis and brain metastasis in the differential diagnosis of melanoma patients receiving CTLA-4 blockade who present this constellation of symptoms.
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PMID:Anti-CTLA-4 therapy-related autoimmune hypophysitis in a melanoma patient. 1951 47