Selecting Optimal Antibody–Drug Conjugate Targets Using Indication‐Dependent or Indication‐Independent Approaches

Harper, Jay; Hollingsworth, Robert E.

doi:10.1002/9781119060727.ch2

Cited by 2 publications

(5 citation statements)

References 54 publications

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“…Therefore, delivering a payload as specifically as possible to cancer cells is of paramount importance for ADC design while attempting to balance factors such as safety and efficacy. Tumour-specific targets can be identified for more than one specific cancer type and sometimes for a range of malignancies [ 44 ].…”

Section: Features Of Antigens For Antibody Target Selection In Adc De...mentioning

confidence: 99%

“…According to the currently accepted dogma, the ideal target antigen for an effective ADC should be expressed with sufficient density and homogeneity on the surface of tumour cells, and with minimal expression on normal cells, to limit on-target off-tumour toxicity and to optimise the therapeutic index [ 14 , 44 , 45 ]. The majority of preclinical and clinical targets for ADCs are tumour-associated rather than tumour-specific [ 44 ], meaning that they are overexpressed by cancer cells and expressed to some extent by normal cells [ 12 , 45 ]. Therefore, an important consideration is whether ADC targets are present and, if so to what extent, in vital or regenerative non-malignant tissues [ 23 , 46 ].…”

Section: Features Of Antigens For Antibody Target Selection In Adc De...mentioning

confidence: 99%

“…In addition to specific and abundant expression, an optimal target antigen also needs to be extracellular in order for the mAb to access the antigenic epitope [ 13 , 15 , 22 , 44 ]. Furthermore, it is accepted that ADC efficacy usually depends on efficient target-mediated internalisation to deliver the cytotoxic payload inside cancer cells, thus making internalisation following mAb binding a particularly important property for ADC target antigens.…”

Section: Features Of Antigens For Antibody Target Selection In Adc De...mentioning

confidence: 99%

“…This is especially evident for ADCs targeted to solid tumours. For example, clinical experience in evaluating the effectiveness of Kadcyla ® against HER2-positive metastatic breast cancer has demonstrated better survival outcomes in high compared with low HER2-expressing subgroups [ 44 , 173 ].…”

Section: Target Selection In the Design Of Adcsmentioning

confidence: 99%

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Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

Esapa

Jiang

Cheung

et al. 2023

Cancers

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Antibody drug conjugates (ADCs) are powerful anti-cancer therapies comprising an antibody joined to a cytotoxic payload through a chemical linker. ADCs exploit the specificity of antibodies for their target antigens, combined with the potency of cytotoxic drugs, to selectively kill target antigen-expressing tumour cells. The recent rapid advancement of the ADC field has so far yielded twelve and eight ADCs approved by the US and EU regulatory bodies, respectively. These serve as effective targeted treatments for several haematological and solid tumour types. In the development of an ADC, the judicious choice of an antibody target antigen with high expression on malignant cells but restricted expression on normal tissues and immune cells is considered crucial to achieve selectivity and potency while minimising on-target off-tumour toxicities. Aside from this paradigm, the selection of an antigen for an ADC requires consideration of several factors relating to the expression pattern and biological features of the target antigen. In this review, we discuss the attributes of antigens selected as targets for antibodies used in clinically approved ADCs for the treatment of haematological and solid malignancies. We discuss target expression, functions, and cellular kinetics, and we consider how these factors might contribute to ADC efficacy.

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Section: Features Of Antigens For Antibody Target Selection In Adc De...mentioning

confidence: 99%

Section: Features Of Antigens For Antibody Target Selection In Adc De...mentioning

confidence: 99%

Section: Features Of Antigens For Antibody Target Selection In Adc De...mentioning

confidence: 99%

Section: Target Selection In the Design Of Adcsmentioning

confidence: 99%

See 2 more Smart Citations

Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

Esapa

Jiang

Cheung

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…The fundamental step of ADC development remains the selection of target-antigen [7,8]. The optimal target-antigen should be characterized by tumor-specific and homogeneous expression pattern, high levels of expression, rapid internalization, and minimal ectodomain shedding.…”

Section: Functional Principles and Essential Components Of Adcs 21 Antigen Selection And Antibodiesmentioning

confidence: 99%

Antibody-Drug Conjugates: Functional Principles and Applications in Oncology and Beyond

et al. 2021

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In the era of precision medicine, antibody-based therapeutics are rapidly enriched with emerging advances and new proof-of-concept formats. In this context, antibody-drug conjugates (ADCs) have evolved to merge the high selectivity and specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of attached payloads. So far, ten ADCs have been approved by FDA for oncological indications and many others are currently being tested in clinical and preclinical level. This paper summarizes the essential components of ADCs, from their functional principles and structure up to their limitations and resistance mechanisms, focusing on all latest bioengineering breakthroughs such as bispecific mAbs, dual-drug platforms as well as novel linkers and conjugation chemistries. In continuation of our recent review on anticancer implication of ADC’s technology, further insights regarding their potential usage outside of the oncological spectrum are also presented. Better understanding of immunoconjugates could maximize their efficacy and optimize their safety, extending their use in everyday clinical practice.

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Selecting Optimal Antibody–Drug Conjugate Targets Using Indication‐Dependent or Indication‐Independent Approaches

Cited by 2 publications

References 54 publications

Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

Antibody-Drug Conjugates: Functional Principles and Applications in Oncology and Beyond

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