Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer.
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.
Blansfield
Joseph A
JA
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1201, USA.
Beck
Kimberly E
KE
Tran
Khoi
K
Yang
James C
JC
Hughes
Marybeth S
MS
Kammula
Udai S
US
Royal
Richard E
RE
Topalian
Suzanne L
SL
Haworth
Leah R
LR
Levy
Catherine
C
Rosenberg
Steven A
SA
Sherry
Richard M
RM
D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy; D060908:CTLA-4 Antigen; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000556:secondary; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010902:Pituitary Gland / Q000187:drug effects* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human