Related Experiment Video
Updated: Oct 18, 2025
Generation of Murine Monoclonal Antibodies by Hybridoma Technology
Published on: January 2, 2017
Generation of Antibody-Drug Conjugate Resistant Models
Lucía Gandullo-Sánchez1, Alberto Ocaña2,3, Atanasio Pandiella1
1Instituto de Biología Molecular y Celular del Cáncer, CSIC, IBSAL and CIBERONC, 37007 Salamanca, Spain.
Abstract:
In the last 20 years, antibody-drug conjugates (ADCs) have been incorporated into the oncology clinic as treatments for several types of cancer. So far, the Food and Drug Administration (FDA) has approved 11 ADCs and other ADCs are in the late stages of clinical development. Despite the efficacy of this type of drug, the tumors of some patients may result in resistance to ADCs. Due to this, it is essential not only to comprehend resistance mechanisms but also to develop strategies to overcome resistance to ADCs. To reach these goals, the generation and use of preclinical models to study those mechanisms of resistance are critical. Some cells or patient tumors may result in primary resistance to the action of an ADC, even if they express the antigen against which the ADC is directed. Isolated primary tumoral cells, cell lines, or patient explants (patient-derived xenografts) with these characteristics can be used to study primary resistance. The most common method to generate models of secondary resistance is to treat cancer cell lines or tumors with an ADC. Two strategies, either continuous treatment with the ADC or intermittent treatment, have successfully been used to develop those resistance models.
Insights
Antibody-drug conjugates (ADCs) are vital cancer treatments, but resistance can occur. Developing preclinical models is crucial for understanding and overcoming ADC resistance in oncology.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Antibody-drug conjugates (ADCs) have become important cancer therapies, with 11 approved by the FDA and others in development.
- Tumor resistance to ADCs is a significant clinical challenge, necessitating research into resistance mechanisms and mitigation strategies.
Purpose of the Study:
- To highlight the critical role of preclinical models in understanding and overcoming antibody-drug conjugate (ADC) resistance.
- To discuss strategies for generating and utilizing models for both primary and secondary ADC resistance.
Main Methods:
- Utilizing isolated primary tumor cells, cell lines, or patient-derived xenografts to study inherent (primary) resistance to ADCs.
- Generating models of acquired (secondary) resistance through continuous or intermittent treatment of cancer cell lines or tumors with ADCs.
Main Results:
- Preclinical models, including those derived from patient samples, are essential for investigating why some tumors resist ADCs despite antigen expression.
- Established methods for inducing secondary resistance provide valuable tools for studying adaptive tumor responses to ADC therapy.
Conclusions:
- Understanding ADC resistance mechanisms through robust preclinical models is key to improving cancer treatment efficacy.
- Developing strategies to overcome resistance is essential for maximizing the therapeutic potential of antibody-drug conjugates in oncology.
More Related Videos
Related Concept Videos
01:31Hybridoma Technology
Hybridoma Selection
Commonly used fusion techniques — electroporation,...
02:56Treatment Resistant Cancers
01:30Development of Antibiotic Resistance