TY - JOUR
T1 - Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer.
AU - Graziani, Grazia
AU - Tentori, L
AU - Navarra, Pierluigi
PY - 2012
Y1 - 2012
N2 - Ipilimumab (Yervoy, developed by Medarex and Bristol-Myers Squibb) is a fully
human monoclonal IgG1κ antibody against the cytotoxic T-lymphocyte antigen-4
(CTLA-4), an immune-inhibitory molecule expressed in activated T cells and in
suppressor T regulatory cells. Interaction of the monoclonal antibody with CTLA-4
blocks inhibitory signals generated through this receptor and enhances T cell
activation, leading to increased antitumor responses. Ipilimumab has been
approved by FDA in March 2011 as monotherapy (3mg/kg every 3 weeks for 4 doses)
for the treatment of advanced (unresectable or metastatic) melanoma both in
pre-treated or chemotherapy naïve patients. Four months later, ipilimumab has
received a rapid approval by the European Commission, after a positive opinion
from the Committee for Medicinal Products for Human Use. However, the indication
in the EU is limited to previously-treated patients with advanced melanoma.
Ipilimumab is the first agent that has demonstrated to improve overall survival
in patients with metastatic melanoma, which has a very poor prognosis, in
randomized phase III clinical trials. The patterns of tumour response to
ipilimumab differ from those observed with cytotoxic chemotherapeutic agents,
since patients may have a delayed yet durable response and obtain long-term
survival benefit despite an initial tumour growth. The major draw-back of
ipilimumab is the induction of immune-related adverse effects; the latter can be
life-threatening, unless promptly managed with immunosuppressive agents (most
frequently corticosteroids) according to specific guidelines. Further development
of ipilimumab includes its use in the neoadjuvant or adjuvant high-risk melanoma
setting and for the treatment of other refractory and advanced solid tumours,
either as single agent or in combination with additional immunostimulating agents
or molecularly targeted therapies.
AB - Ipilimumab (Yervoy, developed by Medarex and Bristol-Myers Squibb) is a fully
human monoclonal IgG1κ antibody against the cytotoxic T-lymphocyte antigen-4
(CTLA-4), an immune-inhibitory molecule expressed in activated T cells and in
suppressor T regulatory cells. Interaction of the monoclonal antibody with CTLA-4
blocks inhibitory signals generated through this receptor and enhances T cell
activation, leading to increased antitumor responses. Ipilimumab has been
approved by FDA in March 2011 as monotherapy (3mg/kg every 3 weeks for 4 doses)
for the treatment of advanced (unresectable or metastatic) melanoma both in
pre-treated or chemotherapy naïve patients. Four months later, ipilimumab has
received a rapid approval by the European Commission, after a positive opinion
from the Committee for Medicinal Products for Human Use. However, the indication
in the EU is limited to previously-treated patients with advanced melanoma.
Ipilimumab is the first agent that has demonstrated to improve overall survival
in patients with metastatic melanoma, which has a very poor prognosis, in
randomized phase III clinical trials. The patterns of tumour response to
ipilimumab differ from those observed with cytotoxic chemotherapeutic agents,
since patients may have a delayed yet durable response and obtain long-term
survival benefit despite an initial tumour growth. The major draw-back of
ipilimumab is the induction of immune-related adverse effects; the latter can be
life-threatening, unless promptly managed with immunosuppressive agents (most
frequently corticosteroids) according to specific guidelines. Further development
of ipilimumab includes its use in the neoadjuvant or adjuvant high-risk melanoma
setting and for the treatment of other refractory and advanced solid tumours,
either as single agent or in combination with additional immunostimulating agents
or molecularly targeted therapies.
KW - Ipilimumab
KW - Ipilimumab
UR - http://hdl.handle.net/10807/7022
U2 - 10.1016/j.phrs.2011.09.002
DO - 10.1016/j.phrs.2011.09.002
M3 - Article
SN - 1043-6618
VL - 65
SP - 9
EP - 22
JO - Pharmacological Research
JF - Pharmacological Research
ER -