Expanding ADC Applications: Beyond Oncology

Introduction

Antibody-drug conjugates (ADCs) have revolutionised cancer treatment by delivering targeted therapies with enhanced efficacy and reduced toxicity. However, their potential extends far beyond oncology. Recent research has demonstrated the versatility of ADCs in treating autoimmune diseases, infectious diseases, and other non-oncological conditions. This blog delves into the expanding applications of ADCs and their transformative potential in medicine [1].

ADCs in Autoimmune Diseases

Autoimmune diseases, characterised by the immune system attacking healthy tissues, require precise therapeutic interventions. Current treatments often involve broad immunosuppressants, which can lead to severe side effects. ADCs offer a targeted approach to modulating immune responses [2].

• Mechanism: ADCs designed to target immune cells, such as B cells or T cells, can deliver immunosuppressive agents directly to overactive immune cells [3].
• Case Study: An ADC targeting CD19 has shown promise in treating systemic lupus erythematosus by depleting B cells while sparing healthy tissues [4].

ADCs in Infectious Diseases

The global rise of antimicrobial resistance has driven the search for innovative solutions. ADCs are emerging as a novel approach to combat infectious diseases:

• Antibiotic-ADC Hybrids: These ADCs link potent antibiotics to antibodies that target bacterial surface proteins, ensuring selective delivery to infected cells [5].
• Antiviral ADCs: ADCs targeting viral proteins, such as those found in HIV or hepatitis B, have demonstrated efficacy in reducing viral loads in preclinical studies [6].

ADCs in Neurological Disorders

Neurological conditions such as Alzheimer’s disease and multiple sclerosis present unique challenges due to the blood-brain barrier (BBB). ADCs are being engineered to cross the BBB and deliver therapies directly to affected regions [7].

• Innovative Engineering: Modifications to antibodies allow ADCs to penetrate the BBB and target specific neuronal markers [8].
• Potential Applications: ADCs targeting amyloid-beta plaques are under investigation for Alzheimer’s disease, offering hope for disease-modifying treatments [9].

Challenges in Non-Oncological ADC Applications

Expanding ADCs beyond oncology involves addressing several hurdles:

Antigen Specificity: Identifying disease-specific antigens for conditions other than cancer is challenging [10].

1. Payload Selection: The cytotoxic payloads used in oncology are unsuitable for non-cancer indications, necessitating the development of new payloads [11].
2. Regulatory Complexity: Non-oncological ADCs require distinct regulatory pathways, complicating the approval process [12].

Future Directions

The future of ADCs in non-oncological applications is promising, with several avenues for exploration:

1. Novel Targets: Advances in proteomics and genomics are enabling the discovery of new antigens for autoimmune and infectious diseases [13].
2. Combination Therapies: ADCs could be combined with other treatments, such as biologics or small molecules, to enhance efficacy [14].
3. AI-Driven Design: Artificial intelligence is being employed to optimise ADC design, including target selection and payload-linker combinations [15].

Conclusion

The expansion of ADCs into non-oncological areas represents a significant opportunity to address unmet medical needs across a range of diseases. By leveraging advances in technology and cross-disciplinary collaboration, ADCs have the potential to transform medicine beyond oncology [16].

References

1. Beck A, Reichert JM. ADC technologies in the 2020s. MAbs. 2021;13(1):1916062.
2. Smith SW. Advances in ADC applications for autoimmune diseases. J Clin Immunol. 2020;40(4):325-35.
3. Lambert JM, Morris CQ. Antibody-drug conjugates for immune modulation. Trends Biotechnol. 2020;38(1):19-28.
4. FDA. ADCs in autoimmune disease clinical trials. [Internet]. Available from: https://www.fda.gov.
5. Liu R, Sun D. Antibiotic-ADC hybrids for antimicrobial resistance. Clin Infect Dis. 2021;72(3):557-65.
6. Seagen. ADC technology in antivirals. [Internet]. Available from: https://www.seagen.com.
7. Beck A. Crossing the blood-brain barrier with ADCs. Nat Rev Drug Discov. 2019;18(8):603-24.
8. Jain N. Advances in ADC engineering for neurological disorders. J Neurochem. 2021;157(6):1458-70.
9. Chari RV. Targeting amyloid-beta with ADCs. Trends Pharmacol Sci. 2020;41(5):345-55.
10. EMA. Challenges in non-oncological ADC development. [Internet]. Available from: https://www.ema.europa.eu.
11. Lambert JM. Payload innovations for non-cancer ADCs. Bioconjug Chem. 2020;31(7):1675-85.
12. FDA. Regulatory pathways for non-oncological ADCs. [Internet]. Available from: https://www.fda.gov.
13. Chari RV. Advances in proteomics for ADC target discovery. Trends Biotechnol. 2021;39(7):700-12.
14. Beck A. Combination therapies with ADCs. Nat Rev Drug Discov. 2020;19(4):239-52.
15. Jain N. AI-driven ADC design. Expert Opin Drug Discov. 2021;16(5):541-50.
16. Liu R. Future perspectives on ADCs in non-oncology. Expert Opin Biol Ther. 2021;21(5):581-9.