TY - JOUR
T1 - What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma?
AU - Robert, Caroline
AU - Ghiringhelli, Francois
PY - 2009/8/1
Y1 - 2009/8/1
N2 - With increasing knowledge of the molecular basis of the immune system and mechanisms of tumor tolerance, novel approaches to treating malignant diseases refractory to standard therapies are being investigated. Monoclonal antibodies (mAbs) that bind cytotoxic T lymphocyte-associated antigen (CTLA)-4 can block inhibitory signals normally generated through this receptor, thus prolonging and sustaining T-cell activation and proliferation. These antibodies are being developed and tested in patients with metastatic melanoma. This article reviews data published or presented at scientific congresses describing the clinical safety and antitumor activity of two different anti-CTLA-4 mAbs: tremelimumab (CP-675,206) and ipilimumab (MDX-010). Overall, although the response rate has not been consistently higher than the response rates associated with other treatments, the induction of durable responses and the favorable safety profile observed with anti-CTLA-4 mAbs are encouraging. However, the true advantage of these new drugs may depend largely on the characterization of predictive biomarkers of activity and subsequent targeting of responsive patients.
AB - With increasing knowledge of the molecular basis of the immune system and mechanisms of tumor tolerance, novel approaches to treating malignant diseases refractory to standard therapies are being investigated. Monoclonal antibodies (mAbs) that bind cytotoxic T lymphocyte-associated antigen (CTLA)-4 can block inhibitory signals normally generated through this receptor, thus prolonging and sustaining T-cell activation and proliferation. These antibodies are being developed and tested in patients with metastatic melanoma. This article reviews data published or presented at scientific congresses describing the clinical safety and antitumor activity of two different anti-CTLA-4 mAbs: tremelimumab (CP-675,206) and ipilimumab (MDX-010). Overall, although the response rate has not been consistently higher than the response rates associated with other treatments, the induction of durable responses and the favorable safety profile observed with anti-CTLA-4 mAbs are encouraging. However, the true advantage of these new drugs may depend largely on the characterization of predictive biomarkers of activity and subsequent targeting of responsive patients.
KW - Biomarkers
KW - Cytotoxic T lymphocyte-associated antigen 4
KW - Melanoma
KW - Metastasis
UR - http://www.scopus.com/inward/record.url?scp=70249083099&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2009-0028
DO - 10.1634/theoncologist.2009-0028
M3 - Review article
C2 - 19648604
AN - SCOPUS:70249083099
SN - 1083-7159
VL - 14
SP - 848
EP - 861
JO - Oncologist
JF - Oncologist
IS - 8
ER -