Antibody-drug conjugates (ADCs) have emerged as one of the most promising advancements in precision oncology, combining targeted delivery with the potency of traditional chemotherapies. Over the last decade, ADCs have gained significant traction, with more therapies being approved and a rapidly expanding development pipeline. While the therapeutic promise of ADCs is clear, success in this space depends on more than just the drug itself — it relies heavily on precise and reliable diagnostic testing.
Why Diagnostics Matter for ADCs
At their core, ADCs work by targeting specific antigens expressed on cancer cells. While this targeted approach offers significant advantages, it also introduces new challenges. Identifying the right antigens, validating their expression, and ensuring patients are appropriately selected for therapy requires advanced diagnostic tools. This is where technologies such as immunohistochemistry (IHC) and next-generation sequencing (NGS) come into play. As ADCs continue to evolve, diagnostic innovation becomes ever more critical, enabling breakthroughs in therapeutic design, regulatory approval, and real-world application.
In the early phases of ADC development, diagnostic testing focuses on validating antigens that can serve as effective therapeutic targets. Clinical trial assays (CTAs) are critical in this stage, assessing the presence and accessibility of target antigens on tumor cells while ensuring minimal expression in healthy tissues. Advances in proteomic and genomic profiling have expanded the universe of potential antigen targets, particularly tumor-specific antigens (TSAs) and neoantigens. These uniquely expressed antigens hold the promise of increasing ADC efficacy and precision, but they also demand sophisticated testing to confirm their clinical relevance. CTAs provide this foundation, offering the data necessary to refine therapeutic candidates and design robust assays that can transition into regulatory submissions and beyond.
As ADCs move from development into clinical trials, the need for precision grows. Companion diagnostics (CDx) play a pivotal role in this phase, ensuring therapies are matched to the patients most likely to benefit. By confirming target antigen expression in tumor tissue, CDx not only optimize patient selection but also align with regulatory requirements for therapies where efficacy depends on antigen presence. With ADCs increasingly targeting complex or variable biomarkers, such as TSAs and neoantigens, the role of CDx is expected to grow significantly in the coming years. These diagnostics can provide supportive data for treatment decisions that are personalized and may result in better outcomes for patients.
Once an ADC reaches the clinic, diagnostic testing continues to play a vital role to help assess safety and effective application. Routine clinical testing confirms antigen expression, monitors patient response, and assesses potential side effects, providing critical insights that inform ongoing treatment decisions. The reliability and scalability of these tests are essential for integrating ADCs into standard oncology care, particularly as their use expands across indications and patient populations.
From preclinical research to regulatory approval and clinical adoption, diagnostic testing underpins every stage of ADC development. For pharmaceutical companies, collaboration with a strong diagnostic partner — one who can navigate the complexities of antigen validation, assay development, and real-world clinical testing — is essential.
A Growing Need for Innovation
As the ADC field evolves, the biomarker landscape is becoming more complex. Emerging targets such as TSAs and neoantigens hold promise for increasing therapeutic precision but require increasingly sophisticated diagnostic solutions. This growing complexity highlights the need for seamless integration of diagnostics into ADC development programs to ensure these therapies reach the right patients.
How Quest Diagnostics Supports ADC Programs
Quest Diagnostics and its PhenoPath Laboratories division provide end-to-end diagnostic support tailored to the needs of ADC developers. "With decades of experience in IHC assay development, regulatory expertise, and a nationwide clinical testing infrastructure, Quest is uniquely positioned to advance ADC programs from early research to clinical implementation," said Thomas Slavin, chief clinical officer of molecular diagnostics at Quest. "Whether you’re exploring novel targets or scaling companion diagnostics to market, having the right diagnostic partner can make the difference in bringing ADCs to patients safely and effectively."
Download the white paper Antibody-Drug Conjugates: Precision Therapeutics Powered by Diagnostic Innovation for a deeper dive into the science of ADCs, the critical role of diagnostic testing, and the capabilities that define an ideal diagnostic partner