The tumor targeting performance of anti-CD166 Probody drug conjugate CX-2009 and its parental derivatives as monitored by <sup>89</sup>Zr-immuno-PET in xenograft bearing mice

Chomet, Marion; Schreurs, Maxime; Nguyen, Margaret; Howng, Bruce; Villanueva, Ruth; Krimm, Michael; Vasiljeva, Olga; Dongen, Guus A.M.S. van; Vugts, Daniëlle J.

doi:10.7150/thno.44334

Cited by 27 publications

(14 citation statements)

References 24 publications

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“…In one study, the tumor-targeting performance of the anti-CD166 Probody-drug conjugate CX-2009, a Probody therapeutic coupled with the toxic drug DM4, was labeled with 89 Zr and evaluated with PET in xenograft-bearing mice (45). CD166 is overexpressed on the outer cell surface of many tumor types but is also present in several healthy organs.…”

Section: Activatable Antibodiesmentioning

confidence: 99%

The Role of ⁸⁹Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals

et al. 2020

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The identification of molecular drivers of disease and the compelling rise of biotherapeutics have impacted clinical care but have also come with challenges. Such therapeutics include peptides, monoclonal antibodies, antibody fragments and nontraditional binding scaffolds, activatable antibodies, bispecific antibodies, immunocytokines, antibody-drug conjugates, enzymes, polynucleotides, and therapeutic cells, as well as alternative drug carriers such as nanoparticles. Drug development is expensive, attrition rates are high, and efficacy rates are lower than desired. Almost all these drugs, which in general have a long residence time in the body, can stably be labeled with 89 Zr for whole-body PET imaging and quantification.Although not restricted to monoclonal antibodies, this approach is called 89 Zr-immuno-PET. This review summarizes the state of the art of the technical aspects of 89 Zr-immuno-PET and illustrates why it has potential for steering the design, development, and application of biologic drugs. Appealing showcases are discussed to illustrate what can be learned with this emerging technology during preclinical and especially clinical studies about biologic drug formats and disease targets. In addition, an overview of ongoing and completed clinical trials is provided. Although 89 Zr-immuno-PET is a young tool in drug development, its application is rapidly expanding, with first clinical experiences giving insight on why certain drugtarget combinations might have better perspectives than others.

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Section: Activatable Antibodiesmentioning

confidence: 99%

The Role of ⁸⁹Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals

et al. 2020

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“…PDCs are masked conjugates that restrict normal tissue recognition and are unmasked by tumor proteases, thereby restricting on-target toxicity outside the tumor site. 83,84 CX-2029, an anti-CD71 PDC, is currently under evaluation in a phase I/II trial for solid tumors or DLBCL (NCT03543813). CX-2009 is an anti-CD166 PDC in a phase I/II trial for unresectable solid tumors (NCT03149549) and a phase II trial to assess activity as a monotherapy or combinational therapy in TNBC (NCT04596150).…”

Section: Novel Adcs In Clinical Trialsmentioning

confidence: 99%

Targeting cancer with antibody-drug conjugates: Promises and challenges

Dean

Luo

Twomey

et al. 2021

mAbs

127

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Antibody-drug conjugates (ADCs) are a rapidly expanding class of biotherapeutics that utilize antibodies to selectively deliver cytotoxic drugs to the tumor site. As of May 2021, the U.S. Food and Drug Administration (FDA) has approved ten ADCs, namely Adcetris®, Kadcyla®, Besponsa®, Mylotarg®, Polivy®, Padcev®, Enhertu®, Trodelvy®, Blenrep®, and Zynlonta™ as monotherapy or combinational therapy for breast cancer, urothelial cancer, myeloma, acute leukemia, and lymphoma. In addition, over 80 investigational ADCs are currently being evaluated in approximately 150 active clinical trials. Despite the growing interest in ADCs, challenges remain to expand their therapeutic index (with greater efficacy and less toxicity). Recent advances in the manufacturing technology for the antibody, payload, and linker combined with new bioconjugation platforms and state-of-the-art analytical techniques are helping to shape the future development of ADCs. This review highlights the current status of marketed ADCs and those under clinical investigation with a focus on translational strategies to improve product quality, safety, and efficacy.

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“…The use of probodies in ADCs to enhance tumor cell-specific delivery of drugs has recently been tested [124]. In this respect, an anti-CD166 probody-drug conjugate has shown on-target on-tumor specificity in a preclinical study on lung cancer [125].…”

Section: Strengths and Weaknesses Of Adcs: Challenges And Perspectivesmentioning

confidence: 99%

Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology

Esnault

Schrama

Houben

et al. 2022

Cancers

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Antibody–drug conjugates (ADCs) are an emerging class of therapeutics, with twelve FDA- and EMA-approved drugs for hematological and solid cancers. Such drugs consist in a monoclonal antibody linked to a cytotoxic agent, allowing a specific cytotoxicity to tumor cells. In recent years, tremendous progress has been observed in therapeutic approaches for advanced skin cancer patients. In this regard, targeted therapies (e.g., kinase inhibitors) or immune checkpoint-blocking antibodies outperformed conventional chemotherapy, with proven benefit to survival. Nevertheless, primary and acquired resistances as well as adverse events remain limitations of these therapies. Therefore, ADCs appear as an emerging therapeutic option in oncodermatology. After providing an overview of ADC design and development, the goal of this article is to review the potential ADC indications in the field of oncodermatology.

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The tumor targeting performance of anti-CD166 Probody drug conjugate CX-2009 and its parental derivatives as monitored by ⁸⁹Zr-immuno-PET in xenograft bearing mice

Cited by 27 publications

References 24 publications

The Role of ⁸⁹Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals

The Role of ⁸⁹Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals

Targeting cancer with antibody-drug conjugates: Promises and challenges

Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology

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The tumor targeting performance of anti-CD166 Probody drug conjugate CX-2009 and its parental derivatives as monitored by 89Zr-immuno-PET in xenograft bearing mice

Cited by 27 publications

References 24 publications

The Role of 89Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals

The Role of 89Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals

Targeting cancer with antibody-drug conjugates: Promises and challenges

Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology

Contact Info

Product

Resources

About

The tumor targeting performance of anti-CD166 Probody drug conjugate CX-2009 and its parental derivatives as monitored by ⁸⁹Zr-immuno-PET in xenograft bearing mice

The Role of ⁸⁹Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals

The Role of ⁸⁹Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals