Antibody-Drug Conjugates

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (31 July 2013) | Viewed by 44377

Special Issue Editor


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Guest Editor
MedImmune, One MedImmune Way, Gaithersburg, MD 20878, USA
Interests: bispecific antibodies; antibody drug conjugates; Fc-engineered antibodies; cancer therapy; antibody targets; recombinant therapeutic proteins; Fc-fusions; single domain antibodies; bi-functional antibody fusion proteins; drug delivery systems; toxins

Special Issue Information

Dear Colleagues,

Antibody-drug conjugates (ADC) represent an innovative therapeutic application that combines the exquisite properties of monoclonal antibodies, with the potent cell killing activity of cytotoxic small molecule drugs, thus reducing systemic toxicity (often seen with small molecule drugs) while increasing the therapeutic benefits for patients. A special issue of Antibodies, with focus on ADC, welcome manuscripts with examples of early and recent ADC, focusing on choosing the right target, choosing the right antibody, choosing the right cytotoxic small molecule warhead, choosing the right linker, choosing the right site of conjugation on the antibody or antibody fragment, and finally putting the ADC all together. Moreover, manuscript describing novel bio-conjugation strategies, methods to stabilize the ADC, toxicities related to ADC and ADC efficacy in both pre- and clinical settings are also welcome.

Dr. Nazzareno Dimasi
Guest Editor

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Keywords

  • antibody-drug conjugates
  • small-molecule drugs/warheads
  • macromolecule toxins/immunotoxins
  • bio-conjugation/antibody modification
  • cysteine- and lysine-mediated conjugation
  • multifunctional bio-conjugation
  • tumor targets/receptors internalization
  • site-specific antibody conjugation
  • maleimide-based conjugation/maleimide modifications
  • stabilized maleimides
  • biofunctional linkers
  • armed antibodies
  • homogeneous conjugation
  • cleavable and un-cleavable linkers
  • toxicities as relate to antibody-drug conjugates
  • efficacy of antibody-drug conjugates

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Published Papers (2 papers)

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Review
Antibody-Directed Phototherapy (ADP)
by Hayley Pye, Ioanna Stamati, Gokhan Yahioglu, M. Adil Butt and Mahendra Deonarain
Antibodies 2013, 2(2), 270-305; https://doi.org/10.3390/antib2020270 - 25 Apr 2013
Cited by 32 | Viewed by 13113
Abstract
Photodynamic therapy (PDT) is a clinically-approved but rather under-exploited treatment modality for cancer and pre-cancerous superficial lesions. It utilises a cold laser or LED to activate a photochemical reaction between a light activated drug (photosensitiser-drug) and oxygen to generate cytotoxic oxygen species. These [...] Read more.
Photodynamic therapy (PDT) is a clinically-approved but rather under-exploited treatment modality for cancer and pre-cancerous superficial lesions. It utilises a cold laser or LED to activate a photochemical reaction between a light activated drug (photosensitiser-drug) and oxygen to generate cytotoxic oxygen species. These free radical species damage cellular components leading to cell death. Despite its benefits, the complexity, limited potency and side effects of PDT have led to poor general usage. However, the research area is very active with an increasing understanding of PDT-related cell biology, photophysics and significant progress in molecular targeting of disease. Monoclonal antibody therapy is maturing and the next wave of antibody therapies includes antibody-drug conjugates (ADCs), which promise to be more potent and curable. These developments could lift antibody-directed phototherapy (ADP) to success. ADP promises to increase specificity and potency and improve drug pharmacokinetics, thus delivering better PDT drugs whilst retaining its other benefits. Whole antibody conjugates with first generation ADP-drugs displayed problems with aggregation, poor pharmacokinetics and loss of immuno-reactivity. However, these early ADP-drugs still showed improved selectivity and potency. Improved PS-drug chemistry and a variety of conjugation strategies have led to improved ADP-drugs with retained antibody and PS-drug function. More recently, recombinant antibody fragments have been used to deliver ADP-drugs with superior drug loading, more favourable pharmacokinetics, enhanced potency and target cell selectivity. These improvements offer a promise of better quality PDT drugs. Full article
(This article belongs to the Special Issue Antibody-Drug Conjugates)
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Antibody Drug Conjugates as Cancer Therapeutics
by Pamela A. Trail
Antibodies 2013, 2(1), 113-129; https://doi.org/10.3390/antib2010113 - 27 Feb 2013
Cited by 85 | Viewed by 30597
Abstract
Monoclonal antibody (MAb) based therapies have achieved considerable success in oncology, primarily when used in combination with cytotoxic drugs. Antibody drug conjugates (ADCs) are a class of therapeutics that harness the antigen-selectivity of MAbs to deliver highly potent cytotoxic drugs to antigen-expressing tumor [...] Read more.
Monoclonal antibody (MAb) based therapies have achieved considerable success in oncology, primarily when used in combination with cytotoxic drugs. Antibody drug conjugates (ADCs) are a class of therapeutics that harness the antigen-selectivity of MAbs to deliver highly potent cytotoxic drugs to antigen-expressing tumor cells. The use of MAb directed delivery can confer a therapeutic index to highly potent cytotoxic drugs, increasing both the efficacy and safety of therapy. Although simple in concept, to achieve the design goal of improved therapeutic efficacy and reduced toxicity, each of the components of an ADC; the MAb, linker and drug need to considered in the context of the targeted antigen, the selectivity of antigen expression and the biology of the tumor type on which the target antigen is expressed. The characteristics of targets, MAbs, linkers and drugs being used in ADC design are discussed. Full article
(This article belongs to the Special Issue Antibody-Drug Conjugates)
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