Coupling of Cyclic Chemotherapeutic Compounds to Immune Gamma-Globulins

DeCarvalho, Sergio; Rand, H. J.; Lewis, Ann

doi:10.1038/202255a0

Cited by 40 publications

(15 citation statements)

References 3 publications

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“…The methodology to conjugate the first chemotherapeutics to antibodies was described more than 50 years ago (Decarvalho et al, 1964), although it took another 40 years before their design became sufficiently advanced to permit ADC clinical licensing. The development of antibody drug conjugates (ADCs), however, has arguably been the immunoconjugate class most propelled by the commercial successes of therapeutic monoclonal antibody technologies.…”

Section: Anti-cd25 Antibody Drug Conjugatesmentioning

confidence: 99%

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

Flynn

Hartley

2017

Br J Haematol

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CD25 (also termed IL2RA) forms one component of the high-affinity heterotrimeric interleukin 2 (IL2) receptor on activated T cells. Its affinity for IL2 and cellular function are tightly regulated and vary in different cell types. The high frequency of CD25 on the surface of many different haematological tumour cells is now well established and, apart from its prognostic significance, CD25 may be present on leukaemic stem cells and enable oncogenic signalling pathways in leukaemic cells. Additionally, high CD25 expression in activated circulating immune cells and Tregs is a factor that has already been exploited by IL2 immunotherapies for treatment of tumours and autoimmune disease. The relative clinical safety and efficacy of administering anti-CD25 radioimmunoconjugates and immunotoxins in various haematological tumour indications has been established and clinical trials of a novel CD25-directed antibody drug conjugate are underway.

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Section: Anti-cd25 Antibody Drug Conjugatesmentioning

confidence: 99%

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

Flynn

Hartley

2017

Br J Haematol

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“…The first ADC was described over 50 years ago (1). Despite setbacks during the evolution of this class of therapeutics, the field has experienced a renaissance, as marked by the recent US Food and Drug Administration (FDA) approvals of Kadcyla® and Adcetris®.…”

Section: Introductionmentioning

confidence: 99%

Antibody Drug Conjugates: Preclinical Considerations

Bornstein

2015

AAPS J

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ABSTRACT. The development path for antibody drug conjugates (ADCs) is more complex and challenging than for unmodified antibodies. While many of the preclinical considerations for both unmodified and antibody drug conjugates are shared, special considerations must be taken into account when developing an ADC. Unlike unmodified antibodies, an ADC must preferentially bind to tumor cells, internalize, and traffic to the appropriate intracellular compartment to release the payload. Parameters that can impact the pharmacological properties of this class of therapeutics include the selection of the payload, the type of linker, and the methodology for payload drug conjugation. Despite a plethora of in vitro assays and in vivo models to screen and evaluate ADCs, the challenge remains to develop improved preclinical tools that will be more predictive of clinical outcome. This review will focus on preclinical considerations for clinically validated small molecule ADCs. In addition, the lessons learned from Mylotarg®, the first in class FDA-approved ADC, are highlighted.

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“…The concept of an ADC arguably was put forth by the German physician Paul Ehrlich, who in 1906 postulated the concept of a "magic bullet" to deliver drugs to specific targets (Strebhardt and Ullrich, 2008); the first application of ADCs as "guided missiles" was implemented many decades later (Decarvalho et al, 1964). The first successful clinical application of this concept was fulfilled even later with the advancement of gemtuzumab ozogamicin (GO, Mylotarg; Pfizer/Wyeth Pharmaceuticals, Philadelphia, PA) (Bross et al, 2001), the first ADC to be approved for clinical use.…”

Section: Introductionmentioning

confidence: 99%

Absorption, Distribution, Metabolism, and Excretion Considerations for the Development of Antibody-Drug Conjugates

Han

Zhao

2014

Drug Metab Dispos

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Antibody-drug conjugates (ADCs) are a class of therapeutics that are designed to deliver potent small-molecule drugs selectively to cells that express a specific target antigen while limiting systemic exposure to the drug. This is accomplished by conjugating a potent drug onto an antibody-based therapeutic with a linker that is exquisitely stable in plasma. The development of an effective ADC requires optimizing a number of design elements and an extensive understanding of absorption, distribution, metabolism/catabolism, and elimination (ADME) processes for the ADC construct. Furthermore, as ADCs are a combination of an antibody and smallmolecule drug, understanding key aspects of the ADME of each individual component is needed. This review aims to provide considerations for the development of ADCs from an ADME point of view.

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Coupling of Cyclic Chemotherapeutic Compounds to Immune Gamma-Globulins

Cited by 40 publications

References 3 publications

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

The emerging role of anti‐CD25 directed therapies as both immune modulators and targeted agents in cancer

Antibody Drug Conjugates: Preclinical Considerations

Absorption, Distribution, Metabolism, and Excretion Considerations for the Development of Antibody-Drug Conjugates

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