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Antibody delivery and dual / multispecific antibody development

Antibody delivery refers to the use of antibodies or their derivatives as carriers to couple or package drugs or other functional molecules, so as to achieve the selective recognition and delivery of a specific target or tissue. Antibody delivery has the following advantages:

1 Antibodies have high specificity and affinity and can bind to target antigens and through immune effects.

2. Mediates cell death or signaling.

3 Antibodies can prolong the circulation of drugs in the blood and reduce the toxicity to normal tissues.

4 Antibodies can improve drug solubility and stability, and overcome some physiological barriers.

5 Antibodies can modulate their immunogenicity and pharmacokinetics by altering their structure or modification.

Antibody delivery can be divided into the following categories:

1. Antibody-coupled drugs (Antibody-Drug Conjugates, ADCs): connect cytotoxic drugs with antibodies through chemical bonds to form a complex with dual functions. When bound to the target antigen, ADCs can be endocytosed into the cell and then release the drug in lysosomes, thereby killing the cells. ADCs are mainly used for cancer treatment. At present, 10 ADCs have been clinically approved, such as Trastuzumab (Trastuzumab emtansine, Kadcyla) for HER 2 positive breast cancer, and Brunzuzumab (Brentuximab vedotin, Adcetris) for Hodgkin lymphoma and peripheral T cell lymphoma.

2. Antibody-coupled enzymes (Antibody-Enzyme Conjugates, AECs): they connect enzymes and antibodies through chemical bonds to form a complex that can catalyze the conversion of a drug precursor into an active drug. When AECs are combined to the target antigen, high concentrations of active drugs can be produced at the target site, thus enhancing the therapeutic efficacy. AECs are also mainly used for cancer treatment, and one AEC has received clinical approval, namely axitimumab (Asparaginase Erwinia chrysanthemi, Erwinaze) in acute lymphoblastic leukemia.

3. Antibody-coupled nucleic acids (Antibody-Nucleic Acid Conjugates, ANCs): they connect nucleic acids with antibodies through chemical bonds to form a complex that can regulate gene expression. When ANCs bind to the target antigen, they can promote the intracellular delivery of nucleic acids and achieve therapeutic effects by silencing or activation of specific genes. ANCs can be used in the treatment of various diseases, and one ANC has obtained clinical approval, namely enotitide (Inotersen sodium, Tegsedi) for hereditary hepatic amyloidosis.

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