Antibody Drug Conjugates for Cancer Therapy
Antibody Drug Conjugates for Cancer Therapy Antibody Drug Conjugates for Cancer Therapy
Efficacy/SafetyFour ways for 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
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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
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