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2016 ; 2
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Antibody Therapeutics in Oncology
#MMPMID27081677
Wold ED
; Smider VV
; Felding BH
Immunotherapy (Los Angel)
2016[Mar]; 2
(1
): ä PMID27081677
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One of the newer classes of targeted cancer therapeutics is monoclonal
antibodies. Monoclonal antibody therapeutics are a successful and rapidly
expanding drug class due to their high specificity, activity, favourable
pharmacokinetics, and standardized manufacturing processes. Antibodies are
capable of recruiting the immune system to attack cancer cells through
complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In
an ideal scenario the initial tumor cell destruction induced by administration of
a therapeutic antibody can result in uptake of tumor associated antigens by
antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of
direct tumor cell killing by antibodies include antibody recognition of cell
surface bound enzymes to neutralize enzyme activity and signaling, or induction
of receptor agonist or antagonist activity. Both approaches result in cellular
apoptosis. In another and very direct approach, antibodies are used to deliver
drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs)
direct cytotoxic compounds to tumor cells, after selective binding to cell
surface antigens, internalization, and intracellular drug release. Efficacy and
safety of ADCs for cancer therapy has recently been greatly advanced based on
innovative approaches for site-specific drug conjugation to the antibody
structure. This technology enabled rational optimization of function and
pharmacokinetics of the resulting conjugates, and is now beginning to yield
therapeutics with defined, uniform molecular characteristics, and unprecedented
promise to advance cancer treatment.
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