Therapeutic potential of antibody-drug conjugates possessing bifunctional anti-inflammatory action in the pathogenesis of rheumatoid arthritis
Abstract In an age where there is a remarkable upsurge in developing precision medicines, antibody-drug conjugates (ADCs) have emerged as a progressive therapeutic strategy. ADCs typically consist of monoclonal antibodies (mAb) conjugated to the cytotoxic payloads by utilizing a linker, combining th...
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BMC
2024-12-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-024-03452-0 |
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| author | Tanu Dixit Anuradha Vaidya Selvan Ravindran |
| author_facet | Tanu Dixit Anuradha Vaidya Selvan Ravindran |
| author_sort | Tanu Dixit |
| collection | DOAJ |
| description | Abstract In an age where there is a remarkable upsurge in developing precision medicines, antibody-drug conjugates (ADCs) have emerged as a progressive therapeutic strategy. ADCs typically consist of monoclonal antibodies (mAb) conjugated to the cytotoxic payloads by utilizing a linker, combining the benefits of definitive target specificity of mAbs and potent killing impact of payload to achieve precise and efficient elimination of target cells. In addition to their well-established role in oncology, ADCs are currently demonstrating encouraging potential in addressing the unmet requirements in the treatment of autoimmune conditions such as rheumatoid arthritis (RA). Prevalent long-term autoimmune disease RA costs billions of dollars annually but still, there is a lack of precision-targeted therapeutics with minimal side effects. This review provides an overview of the RA pathogenesis, pre-existing therapies, and their limitations, the introduction of ADCs in RA treatment, the mechanism of ADCs, and a summary of ADCs in preclinical and clinical trials. Based on the literature we also propose a strategy in ADC synthesis, which may increase the efficiency in targeting multifactorial diseases like RA. We propose to utilize DMARDs (Disease-modifying anti-rheumatic drugs), the first-line treatment for RA, as a payload for ADC synthesis. DMARDs are the only class of medication that limits the disease progression, but their efficacy is limited due to off-target toxicities. Hence, utilizing them as payload will help to deliver them directly at the targeted site, reducing their off-target toxicity, which in turn will increase their efficiency in targeting disease. Also, as mAbs are not sufficient to achieve remission, they are given in combinations with DMARDs. Hence, synthesizing ADCs may reduce the multiple and higher dosages given to patients, which in turn may enhance patient compliance. |
| format | Article |
| id | doaj-art-a1805870bf1a410da8c5002baaea32ff |
| institution | OA Journals |
| issn | 1478-6362 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | Arthritis Research & Therapy |
| spelling | doaj-art-a1805870bf1a410da8c5002baaea32ff2025-08-20T01:47:29ZengBMCArthritis Research & Therapy1478-63622024-12-0126111410.1186/s13075-024-03452-0Therapeutic potential of antibody-drug conjugates possessing bifunctional anti-inflammatory action in the pathogenesis of rheumatoid arthritisTanu Dixit0Anuradha Vaidya1Selvan Ravindran2Symbiosis School of Biological Sciences (SSBS), Faculty of Medical & Health Sciences, Symbiosis International (Deemed University), LavaleSymbiosis School of Biological Sciences (SSBS), Faculty of Medical & Health Sciences, Symbiosis International (Deemed University), LavaleSymbiosis School of Biological Sciences (SSBS), Faculty of Medical & Health Sciences, Symbiosis International (Deemed University), LavaleAbstract In an age where there is a remarkable upsurge in developing precision medicines, antibody-drug conjugates (ADCs) have emerged as a progressive therapeutic strategy. ADCs typically consist of monoclonal antibodies (mAb) conjugated to the cytotoxic payloads by utilizing a linker, combining the benefits of definitive target specificity of mAbs and potent killing impact of payload to achieve precise and efficient elimination of target cells. In addition to their well-established role in oncology, ADCs are currently demonstrating encouraging potential in addressing the unmet requirements in the treatment of autoimmune conditions such as rheumatoid arthritis (RA). Prevalent long-term autoimmune disease RA costs billions of dollars annually but still, there is a lack of precision-targeted therapeutics with minimal side effects. This review provides an overview of the RA pathogenesis, pre-existing therapies, and their limitations, the introduction of ADCs in RA treatment, the mechanism of ADCs, and a summary of ADCs in preclinical and clinical trials. Based on the literature we also propose a strategy in ADC synthesis, which may increase the efficiency in targeting multifactorial diseases like RA. We propose to utilize DMARDs (Disease-modifying anti-rheumatic drugs), the first-line treatment for RA, as a payload for ADC synthesis. DMARDs are the only class of medication that limits the disease progression, but their efficacy is limited due to off-target toxicities. Hence, utilizing them as payload will help to deliver them directly at the targeted site, reducing their off-target toxicity, which in turn will increase their efficiency in targeting disease. Also, as mAbs are not sufficient to achieve remission, they are given in combinations with DMARDs. Hence, synthesizing ADCs may reduce the multiple and higher dosages given to patients, which in turn may enhance patient compliance.https://doi.org/10.1186/s13075-024-03452-0Rheumatoid arthritisInflammationAntibody-drug conjugatesMonoclonal antibodies; Disease modifying anti-rheumatoid drugs; Immunomodulation |
| spellingShingle | Tanu Dixit Anuradha Vaidya Selvan Ravindran Therapeutic potential of antibody-drug conjugates possessing bifunctional anti-inflammatory action in the pathogenesis of rheumatoid arthritis Arthritis Research & Therapy Rheumatoid arthritis Inflammation Antibody-drug conjugates Monoclonal antibodies; Disease modifying anti-rheumatoid drugs; Immunomodulation |
| title | Therapeutic potential of antibody-drug conjugates possessing bifunctional anti-inflammatory action in the pathogenesis of rheumatoid arthritis |
| title_full | Therapeutic potential of antibody-drug conjugates possessing bifunctional anti-inflammatory action in the pathogenesis of rheumatoid arthritis |
| title_fullStr | Therapeutic potential of antibody-drug conjugates possessing bifunctional anti-inflammatory action in the pathogenesis of rheumatoid arthritis |
| title_full_unstemmed | Therapeutic potential of antibody-drug conjugates possessing bifunctional anti-inflammatory action in the pathogenesis of rheumatoid arthritis |
| title_short | Therapeutic potential of antibody-drug conjugates possessing bifunctional anti-inflammatory action in the pathogenesis of rheumatoid arthritis |
| title_sort | therapeutic potential of antibody drug conjugates possessing bifunctional anti inflammatory action in the pathogenesis of rheumatoid arthritis |
| topic | Rheumatoid arthritis Inflammation Antibody-drug conjugates Monoclonal antibodies; Disease modifying anti-rheumatoid drugs; Immunomodulation |
| url | https://doi.org/10.1186/s13075-024-03452-0 |
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