P. Senter

Publications257
h-index59
Citations15,602
Highly Influential Citations480
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Effects of Drug Loading on the Antitumor Activity of a Monoclonal Antibody Drug Conjugate
TLDR
By decreasing drug loading per antibody, the therapeutic index was increased demonstrating that drug loading is a key design parameter for antibody-drug conjugates.
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Arming antibodies: prospects and challenges for immunoconjugates
  • A. Wu, P. Senter
  • Biology, Chemistry
    Nature Biotechnology
  • 1 September 2005
TLDR
For the next generation of immunoconjugates, advances in protein engineering will permit greater control of mAb targeting, clearance and pharmacokinetics, resulting in significantly improved delivery to tumors of radioisotopes and potent anticancer drugs.
View on Nature
Development of potent monoclonal antibody auristatin conjugates for cancer therapy
TLDR
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.
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cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity.
TLDR
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.
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The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma
TLDR
Research is under way to extend the applications of brentuximab vedotin and to advance the field by developing other ADCs with new linker and conjugation strategies.
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Development of potent monoclonal antibody auristatin conjugates for cancer therapy
TLDR
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.
View on Springer
Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity.
TLDR
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.
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CR011, a fully human monoclonal antibody-auristatin E conjugate, for the treatment of melanoma.
TLDR
These preclinical results support the continued evaluation of CR011-vcMMAE for the treatment of melanoma and help identify melanoma-associated cell surface molecules and develop as well as preclinically test immunotherapeutic reagents designed to exploit such targets.
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SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML.
TLDR
Mechanistic studies indicate that the cytotoxic effects of SGN-CD33A involve DNA damage with ensuing cell cycle arrest and apoptotic cell death, and suggest that S GN-CD 33A has CD33-directed antitumor activity and support clinical testing of this novel therapeutic in patients with AML.
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Chemotherapy delivery issues in central nervous system malignancy: a reality check.
TLDR
Because of the difficulty in treating CNS tumors, innovative treatments and alternative delivery techniques involving brain/cord capillaries, choroid plexus, and CSF are needed.
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