The journey of targeted drug conjugates in solid tumors: moving beyond antibody drug conjugates
Stephen Walsh1, Francesca Wood1, Leslie R DeMars2
1BicycleTx Ltd, Cambridge, UK.
Introduction:
Antibody drug conjugates (ADCs) selectively deliver cytotoxins to tumor cells using highly specific monoclonal antibodies. While ADCs are a standard treatment paradigm in oncology, safety- and efficacy-related challenges remain. Additional platforms are needed to deliver more effective targeted therapy with differentiated safety profiles.
Areas Covered:
This narrative review discusses the preclinical and clinical journey of ADCs, their shortcomings, and avenues for refinement. Development of novel antibody fragment-drug conjugates, small molecule-drug conjugates (SMDCs), peptide drug conjugates (PDCs), and Bicycle drug conjugate (BDC) molecules are discussed based on targeted literature searches for each technology described; searches were not bound by specific terms or dates in PubMed or ClinicalTrials.gov.
Expert Opinion:
Targeted delivery of cytotoxins will continue to be a powerful tool against cancer; however, we believe novel SMDCs, PDCs, and BDC molecules will help circumvent current challenges surrounding cytotoxin-containing ADCs and provide differentiated treatment options in solid tumors, including those particularly difficult to treat. We expect promising preclinical and clinical data emerging for SMDCs, PDCs, and BDC molecules will translate into approvals, such as BDC molecules that are under pivotal randomized phase II clinical investigation. These novel treatments will increase survival and quality of life for patients with solid tumors.
Insights
New drug conjugate platforms like small molecule-drug conjugates (SMDCs), peptide drug conjugates (PDCs), and Bicycle drug conjugates (BDCs) offer improved targeted cancer therapy. These novel approaches aim to overcome limitations of antibody drug conjugates (ADCs) for better patient outcomes.
Area of Science:
- Oncology
- Drug Delivery
- Molecular Therapeutics
Background:
- Antibody drug conjugates (ADCs) are established cancer therapies using monoclonal antibodies to deliver cytotoxins.
- Despite ADC success, challenges in safety and efficacy necessitate advanced targeted therapy platforms.
- Novel drug conjugate strategies are crucial for improving treatment outcomes in oncology.
Purpose of the Study:
- To review the development and limitations of ADCs.
- To explore emerging drug conjugate platforms including SMDCs, PDCs, and BDCs.
- To discuss the potential of these novel conjugates in overcoming ADC challenges and improving solid tumor treatment.
Main Methods:
- A narrative review of preclinical and clinical data.
- Targeted literature searches in PubMed and ClinicalTrials.gov for ADC, SMDC, PDC, and BDC technologies.
- Analysis of existing and emerging drug conjugate platforms.
Main Results:
- ADCs face persistent safety and efficacy challenges.
- Novel platforms like SMDCs, PDCs, and BDCs show promise for targeted cancer therapy.
- These emerging conjugates may offer differentiated safety profiles and improved efficacy, especially in solid tumors.
Conclusions:
- Targeted cytotoxin delivery remains vital in cancer treatment.
- SMDCs, PDCs, and BDCs are poised to address current ADC limitations.
- These novel conjugates are expected to yield significant clinical benefits, improving survival and quality of life for cancer patients.
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