Svetlana O. Doronina

TL;DR: The in vitro and in vivo properties of monoclonal antibody (mAb)-drug conjugates consisting of the potent synthetic dolastatin 10 analogs auristatin E (AE) and monomethylaurists E (MMAE), linked to the chimeric mAbs cBR96 and cAC10, illustrate the importance of linker technology, drug potency and conjugation methodology in developing safe and efficacious mAb-drug conjugs for cancer therapy.

TL;DR: CAC10-vcMMAE was highly potent and selective against CD30+ tumor lines but was more than 300-fold less active on antigen-negative cells in SCID mouse xenograft models of anaplastic large cell lymphoma or Hodgkin disease, and was efficacious at doses as low as 1 mg/kg.

TL;DR: Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeValVal-Vil Dap-Phe(MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB as discussed by the authors.

TL;DR: Several new linkers were generated in which various components within the L1 linker were either altered or deleted to optimize the ADC, and one of the most promising linkers contained a noncleavable maleimidocaproyl (L4) spacer between the drug and the mAb.

TL;DR: In this paper, drug-linker-ligand conjugates are disclosed in which a Drug is linked to a Ligand via a peptide-based Linker unit.