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#ADCs

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Immunological Applications

Antibody–drug conjugates (ADCs) combine:

Antibody-drug conjugates integrate precision of biologics with potency of small molecules to overcome poor therapeutic window of conventional chemotherapy that diffuses into all tissues causing systemic toxicity. Monoclonal antibody component provides tumor-selective homing through high affinity binding Kd 10^-9 to 10^-11 M to antigens preferentially expressed on malignant cells ten to hundred fold over normal tissues, such as HER2, CD30, CD22, and internalization via receptor mediated endocytosis clathrin dependent trafficking to early endosome then late endosome fusing with lysosome pH 4.5 c

Ref: Beck et al Nat Rev Drug Discov 2017 16:315 ADC linker payload MMAE DM1; Trail Cancer Immunol Res auristatin maytansine.

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Immunological Applications

Antibody–drug conjugates (ADCs) combine:

Antibody-drug conjugates engineered targeted chemotherapy combining precision monoclonal antibody recognition lethal payload potency too toxic systemic administration alone narrow therapeutic index causing severe myelosuppression neuropathy. Monoclonal antibody component typically humanized IgG1 kappa 150 kDa produced CHO cells reduced fucosylation enhancing Fc gamma receptor affinity binds tumor-associated antigen nanomolar affinity CD30 120 kDa TNFRSF8 Hodgkin Reed-Sternberg anaplastic large cell HER2 185 kDa tyrosine kinase amplified breast adenocarcinoma CD33 67 kDa sialic acid-binding Ig-

Ref: FDA Guidance Antibody Drug Conjugates 2020 Principles; Nature Reviews Drug Discovery ADC Technology Evolution 2022; Trail et al Antibody Drug Conjugates Design Development.

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