Fc-mediated mechanisms complement-dependent cytotoxicity (CDC) is considered to be particularly important for successful therapeutic intervention. https://www.creativebiolabs.net/cdc-enhanced-antibody_77.htm

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the immune-effector cells to lyse the target cell. mAb coated target cells can induce the production and
release of cytokines by immune effector cells that express FcRs. Antigen expressing cells can be attacked
by effector cells leading to cell destruction and depletion, which exceed the signaling inhibition effect in
vivo. The ADCC activity of antibodies can be increased by glycosylation or protein engineering of the Fc
region to increase the affinity to FcR. For example, a fucosylation of a chimeric antibody targeting CC-
chemokine receptor 4 (CCR4) increased its in vitro ADCC activity and in vivo antitumor activity. Lately, a
glyco-engineered anti-CD20 antibody, GA101, was developed with increased ADCC activity.
CDC (Complement-dependent cytotoxicity).The first study demonstrating the very potent ability of CDC
to enhance antibody-mediated cytolysis was carried out more than a century ago. CDC is triggered when
the C1 complex binds the antibody- antigen complex, activating a cascade of complement proteins, and
causing a complex to form that attacks the membrane. This results in lysis of the target cell. We now
know that some (but not all) mAbs can mediate CDC. The ability of a given mAb to fix complement and
to induce CDC is partly dependent on antigen concentration, the orientation of the antigen in the
membrane, and whether the antigen is present on the surface as a monomer or a polymer. Meanwhile,
many studies exploring CDC use serum as a source of complement, which highlights the importance of
CDC in the circulation. Indeed, CDC seems to contribute most to the therapeutic effect of mAb in
haematological malignancies, in which target cells are exposed to complement in the circulation.
However, complement binding to target cells does not necessarily result in the lysis of the target cell as
validated anti-cd20 mAb binding a circulating chronic lymphocytic leukaemia. It is generally accepted
that CMC has a limited role in the efficacy of mAbs that recognize target antigens on malignancies
outside the vascular compartment: that is, solid tumors.
Immune system modulators for cancer immunotherapy - Altering the host response.
T cell checkpoint blockade. In recent years, therapeutic antibodies targeted to various immune checkpoint
molecules have progressed from preclinical studies to clinical deployment with impressive results.
These checkpoint blockade antibodies do not target tumor cells directly but instead inhibit pathways
that suppress T cell-mediated antitumor responses, which evolve in parallel with the tumor. Tumor
necrosis can release antigens that are captured and presented as peptide–MHC molecules on antigen-
presenting cells (APCs). Recognition of presented antigens by TCRs and subsequent activation of T cells
can lead to adaptive tumor immunity. Multiple ligand–receptor interactions between T cells and APCs
regulate T cell response by providing either co-stimulatory or inhibitory signals.