Cytotoxic
T-lymphocyte antigen-4 (CTLA-4) plays important role in the T-cell regulation at an early
stage of naive T-cell activation, primarily in the lymph nodes. CTLA-4 has
emerged as an attractive cancer immunotherapy as a part of “immune checkpoint
blockade”. CTLA-4 pathway inhibitors enhance T-cell activation and amplify
T-cell proliferation. Successful results of immune checkpoint inhibitors in
cancer immunotherapy has led to the development of many new agents and
strategies, including combination for the treatment of various cancers.
Despite of
many advancements in the development of anti-cancer therapies, cancer is still
one of the major causes of deaths, globally. Combination therapies are proving
to be more efficient than monotherapy for the treatment of cancer. Studies have
demonstrated that concurrent PD-1 and CTLA-4 blockade have shown positive
results in patients with advanced melanoma. This provides huge opportunities
for development of better combinatorial immunotherapeutic therapies for
checkpoint blockade with molecular targeted therapies, angiogenesis inhibition
and novel vaccines.
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Agenus Inc.
is in the process of developing AGEN1884 as a monoclonal antibody which acts as
a CTLA-4 inhibitor for the treatment of non-small cell lung cancer. It is also
being studied in combination with pembrolizumab, for the treatment of cancer.
Some of the other companies having pipeline of CTLA-4 inhibitor include
AstraZeneca PLC, ImmunOs Therapeutics AG, Tikcro Technologies Ltd.
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