Antibody Drug Conjugates for Cancer Therapy

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Efficacy/SafetyFour ways <strong>for</strong> armed antibodies to kill cellsdrug1. 2.drugNon specific uptakeof intact ADC/TDCdamagedruguptakedamagedruguptakeCells with target3. 4.damagedrugdrugLiver, lung, kidney, etcdamageUptake of releasedfree drugdrugdrugBone marrow cells
Stability impacts SafetyTwo types of armed antibody instabilityPK Her-MC-vc-PAB-MMAE of antibody (8 D/Ab), and Her-MC-vc-PAB-MMAE antibody-drug (5 D/Ab) in Rats conjugate2 mg/kg100Conc. µg/ml101Herceptin-vcMMAE(5:1 drug:MAb ratio)Total MAb0.1Herceptin-vcMMAE(8:1 drug:MAb ratio)0.010 7 14 21 28daysTime (days)1. The drug is released from intact antibodyMAb-drug conjugate2. The drug is released upon catabolism of the antibody
Page 1 and 2: Antibody Drug Conjugates for Cancer
Page 3: Target Screening- Large scale mRNA-
Page 6 and 7: Naked antibodies are likely to be i
Page 9 and 10: How many xenograft models should we
Page 11 and 12: RelativeTenB2 expression in human p
Page 13 and 14: Antibodies armed with auristatinsAN
Page 15: MRP4 (multi drug resistance protein
Page 18 and 19: Structure of the MUC16 antigen and
Page 20 and 21: Endothelin B receptor: A target for
Page 22 and 23: Melanocytes and EDNBR staining in n
Page 24 and 25: Increased cell killing in vitro wit
Page 26 and 27: ETBR Expression in Cell Lines versu
Page 30 and 31: Antibody doses are normalized to dr
Page 32 and 33: In Vivo Efficacy is Retained With T
Page 34 and 35: Cumulative toxicity from long-lived
Page 36: • GNE ADC Team- Susan Spencer- Ke

Antibody Drug Conjugates for Cancer Therapy

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