A Novel Targeted Approach to Achieve Immune System Reset: CD45-Targeted Antibody Drug Conjugates Enable Autologous HSCT and Ameliorate Disease in Preclinical Autoimmune Disease Models

Gillard, Geoffrey O.; Proctor, Jennifer L.; Brooks, Melissa; Lamothe, Tahirih L.; Hyzy, Sharon L.; McDonough, Sean M.; Clark, Nicholas; Palchaudhuri, Rahul; Bhat, Anjali; Sarma, Ganapathy N.; Bhattarai, Prashant; Sawant, Pranoti; Pearse, Bradley R.; McDonagh, Charlotte F.; Boitano, Anthony E.; Cooke, M.

doi:10.1016/j.bbmt.2019.12.407

Cited by 2 publications

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“…TCZ-ALD blocks the IL-6R activity and macrophages activity in the manifestation of RA symptoms and joint inflammation ( Lee et al, 2017 ). A few years later, Gillard et al achieved immune reset of disease-causing reactive T cells by a single administration of CD45-ADC and bone marrow transplantation, resulting in significant disease-modifying effect in mouse models of autoimmune disease ( Gillard et al, 2020 ). In addition, a few studies also addressed the use of ADCs in cardiovascular ( Lim et al, 2015 ) and renal diseases ( Kvirkvelia et al, 2015 ), highlighting the potential application of this therapeutic strategy in other pathological conditions.…”

Section: Adcs Consist Of Antibodies Linked To Cytotoxic Payloads Via ...mentioning

confidence: 99%

A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy

Riccardi,

Dal Bo,

Macor

et al. 2023

Front. Pharmacol.

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Antibody-Drug Conjugates (ADCs) represent an innovative class of potent anti-cancer compounds that are widely used in the treatment of hematologic malignancies and solid tumors. Unlike conventional chemotherapeutic drug-based therapies, that are mainly associated with modest specificity and therapeutic benefit, the three key components that form an ADC (a monoclonal antibody bound to a cytotoxic drug via a chemical linker moiety) achieve remarkable improvement in terms of targeted killing of cancer cells and, while sparing healthy tissues, a reduction in systemic side effects caused by off-tumor toxicity. Based on their beneficial mechanism of action, 15 ADCs have been approved to date by the market approval by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and/or other international governmental agencies for use in clinical oncology, and hundreds are undergoing evaluation in the preclinical and clinical phases. Here, our aim is to provide a comprehensive overview of the key features revolving around ADC therapeutic strategy including their structural and targeting properties, mechanism of action, the role of the tumor microenvironment and review the approved ADCs in clinical oncology, providing discussion regarding their toxicity profile, clinical manifestations and use in novel combination therapies. Finally, we briefly review ADCs in other pathological contexts and provide key information regarding ADC manufacturing and analytical characterization.

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Section: Adcs Consist Of Antibodies Linked To Cytotoxic Payloads Via ...mentioning

confidence: 99%

A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy

Riccardi,

Dal Bo,

Macor

et al. 2023

Front. Pharmacol.

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“…Lumoxiti (moxetumomab pasudotox-tdfk), approved in 2018, is composed of only the variable domains, or antigen-binding domains, of an anti-CD22 mAb fused to a shortened form of the pseudomonas exotoxin, PE38, that inhibits protein synthesis [ 5 ]. A large number of ADCs are currently under clinical development for oncology indications that include various hematological malignancies and solid tumors as well as for targeted therapy in several autoimmune diseases, including multiple sclerosis [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Considerations for the Nonclinical Safety Evaluation of Antibody–Drug Conjugates

Fisher

2021

Antibodies

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The targeted delivery of drugs by means of linking them to antibodies (Abs) to form antibody–drug conjugates (ADCs) has become an important approach in oncology and could potentially be used in other therapeutic areas. Targeted therapy is aimed at improving clinical efficacy while minimizing adverse reactions. The nonclinical safety assessment of ADCs presents several unique challenges involving the need to examine a complex molecule, each component of which can contribute to the effects observed, in appropriate animal models. Some considerations for the nonclinical safety evaluation of ADCs based on a literature review of ADCs in clinical development (currently or previously) are discussed.

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A Novel Targeted Approach to Achieve Immune System Reset: CD45-Targeted Antibody Drug Conjugates Enable Autologous HSCT and Ameliorate Disease in Preclinical Autoimmune Disease Models

Cited by 2 publications

References 0 publications

A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy

A comprehensive overview on antibody-drug conjugates: from the conceptualization to cancer therapy

Considerations for the Nonclinical Safety Evaluation of Antibody–Drug Conjugates

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