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Anti-drug antibodies in the current management of cancer

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Abstract

Monoclonal antibodies (mAbs) have become one of the main therapeutic weapons in modern oncology, mainly as targeted therapies, and immune checkpoint inhibitors. The generation of anti-drug antibodies (ADAs) after their administration can alter their pharmacokinetic, pharmacodynamic, efficacy and safety profile causing infusion-related reactions. Several risk factors have been associated with ADAs development, notably host genetics and immune status, comorbidity, concomitant medications, mAbs molecular structure, dose and route of administration. ADAs are not usually tested on daily clinical practice, being their analysis generally placed in early stages of drug development. ELISA-type assay the most common method. ADAs detection can involve important implications for treatment strategies of cancer patients, guiding therapeutic adjustment. In oncology, some studies about ADAs synthesis related to targeted therapies and immune checkpoint inhibitors have been recently published. Several strategies are proposed to reduce mAbs immunogenicity, such as different schedules, routes of administration or even the use of immunosuppressants. Another question that arises in relation to ADAs generation is the need to measure the concentration levels of active drug to guide the administration schedule. In this review, we will discuss all the aspects that are currently under discussion in relation with ADAs in oncology.

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Acknowledgements

The authors or this manuscript acknowledge to Dr. José Ignacio Chacón, Medical Oncologist of Medical Oncology Department in Hospital Virgen de la Salud, his contribution on the education of new oncologist residents. He has always been open to help and guide clinical and researching projects. We also would like to acknowledge to Dr. Elia Martínez. She is the light leading this review and many other researching activities and on-going projects.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Medical Oncology, Hospital Virgen de la Salud de Toledo, Toledo, Spain

    Miguel Borregón, Alba Ramos, Irene Ramos, Beatriz Berzal & Manuel Mazariegos

  2. Medical Oncology, Hospital General de Segovia, Segovia, Spain

    Katherine Martínez

  3. Medical Oncology, Hospital Universitario de Fuenlabrada, Madrid, Spain

    Elia Martínez

  4. START Madrid-FJD, Early Phase Clinical Trials Unit, Hospital Universitario Fundación Jiménez Díaz, Avda. de los Reyes Católicos, 2, 28040, Madrid, Spain

    Tatiana Hernández, Bernard Doger & Víctor Moreno

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  1. Miguel Borregón
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Borregón, M., Martínez, K., Ramos, A. et al. Anti-drug antibodies in the current management of cancer. Cancer Chemother Pharmacol 89, 577–584 (2022). https://doi.org/10.1007/s00280-022-04418-2

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