Beyond Cancer: Exploring Non-Oncological Applications of ADCs

Introduction

Antibody-drug conjugates (ADCs) have traditionally been associated with cancer treatment, but their potential applications extend far beyond oncology. By modifying their design and payloads, ADCs are now being investigated for use in autoimmune diseases, infectious diseases, and other non-oncological conditions. This blog examines these emerging applications and the unique challenges associated with repurposing ADCs [1].

ADCs in Autoimmune Diseases

Autoimmune diseases, such as rheumatoid arthritis, lupus, and multiple sclerosis, result from an overactive immune system attacking healthy tissues. Current treatments often rely on broad immunosuppression, which can lead to severe side effects, including increased susceptibility to infections [2]. ADCs offer a more targeted approach:

• Mechanism: ADCs designed to target immune cells, such as B cells or T cells, can deliver immunosuppressive payloads specifically to overactive immune cell populations [3].
• Example: ADCs targeting CD20 or CD38 are being evaluated for conditions like systemic lupus erythematosus and multiple sclerosis [4].

By reducing off-target effects, ADCs may offer a safer alternative to traditional therapies [5].

ADCs in Infectious Diseases

The global rise of antibiotic-resistant bacteria has prompted the search for innovative therapeutic strategies. ADCs are being explored as a solution in this context [6]:

• Antibiotic-ADC Hybrids: These ADCs link potent antibiotics to antibodies that specifically bind bacterial surface proteins, ensuring the antibiotic is delivered directly to the infection site [7].
• Antiviral Applications: ADCs targeting viral antigens, such as those on HIV or hepatitis B virus-infected cells, are under investigation for their potential to reduce viral load while sparing uninfected cells [8].

Challenges in Repurposing ADCs

Adapting ADCs for non-oncological diseases comes with its own set of challenges:

1. Antigen Specificity: Unlike cancer, where tumour-specific antigens are relatively well-characterised, non-oncological diseases may lack highly specific targets [9].
2. Payload Modification: Cytotoxic payloads used in oncology may not be suitable for infectious or autoimmune diseases. Instead, payloads must be re-engineered to deliver antibiotics, antivirals, or immunomodulators [10].
3. Regulatory Hurdles: Repurposing ADCs for non-cancer indications requires extensive clinical validation, as safety profiles may differ significantly [11].

Future Directions

The expansion of ADC applications beyond oncology is a promising area of research. Future efforts are likely to focus on:

• Target Discovery: Advances in proteomics and genomics will aid in identifying novel antigens specific to non-oncological diseases [12].
• Optimised Payloads: The development of non-cytotoxic payloads tailored to autoimmune and infectious diseases [13].
• Combination Therapies: Combining ADCs with other treatments, such as small molecules or biologics, to enhance efficacy [14].

Conclusion

Antibody-drug conjugates are poised to revolutionise the treatment of non-oncological diseases, offering targeted therapies with fewer side effects. As research progresses, ADCs have the potential to address unmet medical needs across a wide range of conditions [15].

References

1. Chari RV. Expanding applications of ADCs. Trends Biotechnol. 2021;39(7):700-12.
2. Beck A, Wurch T. ADCs in autoimmune diseases. Nat Rev Drug Discov. 2016;15(2):147-8.
3. Jain N, Smith SW. ADCs targeting immune cells. J Control Release. 2018;269:20-9.
4. Lambert JM, Morris CQ. Antibody-drug conjugates for immune modulation. Trends Biotechnol. 2020;38(1):19-28.
5. Liu R, Sun D. Safety profiles of ADCs in autoimmune applications. Clin Immunol. 2019;207:15-24.
6. Teicher BA, Chari RV. ADCs in infectious diseases. J Antimicrob Chemother. 2018;73(2):291-6.
7. FDA. ADC approvals for infectious diseases. [Internet]. Available from: https://www.fda.gov.
8. Seagen. ADC technology in antivirals. [Internet]. Available from: https://www.seagen.com.
9. Smith SW. Challenges in ADC antigen discovery. Drug Discov Today. 2020;25(5):879-86.
10. Beck A. Payload modification for ADCs. Nat Biotechnol. 2019;37(8):805-15.
11. Lambert JM. Regulatory considerations for non-oncological ADCs. Trends Biotechnol. 2020;38(12):1265-76.
12. Chari RV. Advances in ADC target discovery. Trends Pharmacol Sci. 2021;42(3):165-74.
13. FDA. Guidance on ADC applications. [Internet]. Available from: https://www.fda.gov.
14. Jain N. Combination therapies with ADCs. J Clin Pharmacol. 2019;59(9):1185-92.
15. Liu R. The future of ADCs in non-oncology. Expert Opin Biol Ther. 2021;21(5):581-9.