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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 Nature
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.
View on PubMed
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
Functional analysis of domains II, Ib, and III of Pseudomonas exotoxin.
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The anti-CD30 monoclonal antibody SGN-30 promotes growth arrest and DNA fragmentation in vitro and affects antitumor activity in models of Hodgkin's disease.
TLDR
SGN-30 is being developed for the treatment of patients who have HD that is refractory to initial treatment or who have relapsed and have limited therapeutic options and is able to inhibit the growth of HD cell lines in vitro.
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Efficient Elimination of B-Lineage Lymphomas by Anti-CD20–Auristatin Conjugates
TLDR
Data indicate that anti-CD20–based antibody-drug conjugates are effective antitumor agents when prepared with a stable, enzyme-cleavable peptide linkage to highly potent cytotoxic agents such as MMAE.
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Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells.
TLDR
Evidence is provided that IL6 and its receptor may play an important role in human prostate cancer by examining their sensitivity to the cytotoxic effects of a chimeric toxin composed of IL 6 and Pseudomonas exotoxin.
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Prevention of immunotoxin-mediated vascular leak syndrome in rats with retention of antitumor activity.
TLDR
In rats, intravenous administration of the single-chain immunotoxin BR96 sFv-PE40 results in symptoms that closely resemble VLS seen in human immunotoxins trials, and the use of prophylactic corticosteroids should be considered for Immunotoxin clinical trials, since it may improve therapeutic efficacy by decreasing the dose-limiting toxicity of VLS.
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Monoclonal antibody C242-Pseudomonas exotoxin A. A specific and potent immunotoxin with antitumor activity on a human colon cancer xenograft in nude mice.
TLDR
Two immunotoxins constructed by chemically coupling the monoclonal antibody C242 to Pseudomonas exotoxin A or a modified form, NlysPE40, that lacks the cell binding domain of PE exhibited a strong antitumor effect on a human colon cancer xenograft grown in nude mice.
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Targeted toxins as anticancer agents
TLDR
Using immunotoxin therapy, total regression of established tumors in animal xenograft models have been demonstrated and the results suggest that Immunotoxin molecules offer exciting opportunities for the treatment of human cancer.
View on Wiley
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