The concept is to marry cytotoxic chemotherapy and antibody specificity to overcome the limitations of the respective component technologies.
ADC‘s combine a monoclonal antibody, a toxin and a linker.
Cytotoxic chemotherapy suffers from a lack of specificity.
Antibody therapy has significant specificity but limited potency in its ability to kill target cells.
ADC conceptionally combines these two technologies to obtain maximum benefit.
And anti-body binds to the cancer cell, and the ADC becomes internalized.
When the ADC becomes internalized, it enters the vesicle of the cell, it is digested and the link releases the toxin into the cancer cell.
ADCc ‘s are designed to deliver potent cytotoxic agents directly to tumors by aiming at overexpressed epitopes.
This approach reduces normal tissue exposure making ADC treatment well tolerated and increases clinical benefit.
Antibodies can be used to direct cytotoxic agents to the tumor cell and diminish side effect profile while delivering a more potent therapeutic agent to control the target and the side effects.
ADC technology has four components:1, the cancers or target antigen, 2, the antibody to that target, 3, the linker connecting the drug to be antibody and 4, the drug itself.
An antibody-drug conjugate is as effective as its weakest link, and each component must work perfectly to function satisfactorily.
Optimally the target antigen should be present on the cell surface and should be an internalizing antigen so that, after binding, that ADC is transported into the cell where the cytotoxic agents can exert its effects.
The payload must be highly toxic at very low concentrations.
Newer ADCs have membrane permeable payloads, allowing toxin to leak out of its target, killing nearby tumor cells.
Such a bystander effect is hypothesized for the efficacy of trastusumab deruxtecan in HER2 low breast cancer disease.
Currently the approved therapeutics target The CD33, CD30, CD20, CD79b, and HER2 receptors are approved to treat patients with certain types of leukemia, lymphoma, and breast cancer.
ADC goal is to act similar to a smart bomb where the anti-body component of the drug is specific for a certain type of cancer cell that will allow the drug target that cell and then drop the cytotoxic drug payload attached to it.
Gemtuzumab ozogamamicin a monoclonal antibody target in CD33 linked with calicheamicin is used for the treatment adults with CD33 positive AML.
Brentuximab vedotin consists of the chimeric monoclonal antibody brentuximab linked with the anti-mitotic agent monomethyl auristatin E for the treatment of patients with Hodgkin’s lymphoma.
Polatuzumab vedotin-piiq a monoclonal antibody against CD79b linked with momomethyl auristatin E is used in combination weird rituximab for refractory or relapsed large B cell diffuse lymphoma.
Inotuzumab ozogamicin a humanized anti-CD 22 monoclonal antibody paired with calicheamicin for relapsed B cell precursor ALL.
Ado-trastuzumab Is an anti-HER2 monoclonal antibody trastuzumab linked with emtansine for HER2 positive breast cancer.
Enfortumab vedotin A monoclonal antibody that links with monomethyl auristatin E for urothelial cancer.
Trastuzumab deruxtecan just composed of a anti-HER2 antibody linked with cytotoxic topoisomerase I inhibitor for HER2 positive breast cancer.
Trastuzumab emtansine (T-DM1) targets the HER2 receptor.
The deruxtecan ADC Is composed of the cleavable glycine-glycine-phenylene-glycine tetrapeptide based linker, a self-immolative amino methylene spacer, and a novel topoisomerase 1 inhibitor payload that is a derivative of exatecan.
Sacituzumab govitecan is therapeutically effective for breast cancer and other epithelial malignancies.