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Antibody drug conjugates in gastrointestinal cancer: From lab to clinical development
Davinder Singh1, Divya Dheer1, Abhilash Samykutty2
1Natural Products and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu 180001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Abstract:
The antibody-drug conjugates (ADCs) are one the fastest growing biotherapeutics in oncology and are still in their infancy in gastrointestinal (GI) cancer for clinical applications to improve patient survival. The ADC based approach is developed with tumor specific antigen, antibody carrying cytotoxic agents to precisely target and deliver chemotherapeutics at the tumor site. To date, 11 ADCs have been approved by US-FDA, and more than 80 are in the clinical development phase for different oncological indications. However, The ADCs based therapies in GI cancers are still far from having high-efficient clinical outcomes. The limited success of these ADCs and lessons learned from the past are now being used to develop a newer generation of ADC against GI cancers. In this review, we did a comprehensive assessment of the key components of ADCs, including tumor marker, antibody, cytotoxic payload, and linkage strategy, with a focus on technical improvement and some future trends in the pipeline for clinical translation. The various preclinical and clinical ADCs used in gastrointestinal malignancies, their target, composition and bioconjugation, along with preclinical and clinical outcomes, are discussed. The emphasis is also given to new generation ADCs employing novel mAb, payload, linker, and bioconjugation methods are also included.
Insights
Antibody-drug conjugates (ADCs) show promise in oncology but have limited success in gastrointestinal (GI) cancers. This review assesses key ADC components and future trends for improved GI cancer treatment.
Area of Science:
- Oncology
- Biotherapeutics
- Gastrointestinal Cancer Research
Background:
- Antibody-drug conjugates (ADCs) are rapidly advancing biotherapeutics in oncology.
- ADCs are underutilized in gastrointestinal (GI) cancers, with limited clinical success to date.
- Current ADC therapies for GI cancers require significant improvement for better patient outcomes.
Purpose of the Study:
- To provide a comprehensive review of antibody-drug conjugates (ADCs) for GI cancer treatment.
- To assess key ADC components: tumor markers, antibodies, payloads, and linkage strategies.
- To explore technical improvements and future trends for clinical translation of ADCs in GI malignancies.
Main Methods:
- Comprehensive assessment of existing literature on ADCs in oncology and GI cancers.
- Analysis of preclinical and clinical ADCs, including targets, composition, and bioconjugation.
- Evaluation of technical improvements and novel strategies for next-generation ADCs.
Main Results:
- 11 ADCs approved by US-FDA, with over 80 in clinical development for various cancers.
- ADCs in GI cancers face challenges, necessitating the development of newer generations.
- Review highlights advancements in tumor markers, antibodies, payloads, linkers, and bioconjugation.
Conclusions:
- Next-generation ADCs incorporating novel components and bioconjugation methods offer future potential for GI cancer therapy.
- Further research and development are crucial to overcome current limitations and enhance clinical efficacy.
- Optimizing ADC design and application is key to improving survival rates in GI cancer patients.
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