Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines
Rheumatoid arthritis (RA) is recognized as an autoimmune joint disease driven by T cell responses to self (or modified self or microbial mimic) antigens that trigger and aggravate the inflammatory condition. Newer treatments of RA employ monoclonal antibodies or recombinant receptors against cytokin...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1334281/full |
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| author | Daniel H. Zimmerman Zoltan Szekanecz Adrienn Markovics Kenneth S. Rosenthal Roy E. Carambula Katalin Mikecz |
| author_facet | Daniel H. Zimmerman Zoltan Szekanecz Adrienn Markovics Kenneth S. Rosenthal Roy E. Carambula Katalin Mikecz |
| author_sort | Daniel H. Zimmerman |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) is recognized as an autoimmune joint disease driven by T cell responses to self (or modified self or microbial mimic) antigens that trigger and aggravate the inflammatory condition. Newer treatments of RA employ monoclonal antibodies or recombinant receptors against cytokines or immune cell receptors as well as small-molecule Janus kinase (JAK) inhibitors to systemically ablate the cytokine or cellular responses that fuel inflammation. Unlike these treatments, a therapeutic vaccine, such as CEL-4000, helps balance adaptive immune homeostasis by promoting antigen-specific regulatory rather than inflammatory responses, and hence modulates the immunopathological course of RA. In this review, we discuss the current and proposed therapeutic products for RA, with an emphasis on antigen-specific therapeutic vaccine approaches to the treatment of the disease. As an example, we describe published results of the beneficial effects of CEL-4000 vaccine on animal models of RA. We also make a recommendation for the design of appropriate clinical studies for these newest therapeutic approaches, using the CEL-4000 vaccine as an example. Unlike vaccines that create or boost a new immune response, the clinical success of an immunomodulatory therapeutic vaccine for RA lies in its ability to redirect autoreactive pro-inflammatory memory T cells towards rebalancing the “runaway” immune/inflammatory responses that characterize the disease. Human trials of such a therapy will require alternative approaches in clinical trial design and implementation for determining safety, toxicity, and efficacy. These approaches include adaptive design (such as the Bayesian optimal design (BOIN), currently employed in oncological clinical studies), and the use of disease-related biomarkers as indicators of treatment success. |
| first_indexed | 2024-03-07T14:30:31Z |
| format | Article |
| id | doaj.art-e4aec4b93f5348f99a094ae2c4a12b9e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-07T14:30:31Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e4aec4b93f5348f99a094ae2c4a12b9e2024-03-06T05:13:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13342811334281Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccinesDaniel H. Zimmerman0Zoltan Szekanecz1Adrienn Markovics2Kenneth S. Rosenthal3Roy E. Carambula4Katalin Mikecz5CEL-SCI Corporation, Vienna, VA, United StatesDepartment of Rheumatology, Faculty of Medicine, University of Debrecen, Debrecen, HungaryDepartment of Orthopedic Surgery and Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Basic Sciences, Augusta University/University of Georgia Medical Partnership, Athens, GA, United StatesCEL-SCI Corporation, Vienna, VA, United StatesDepartment of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United StatesRheumatoid arthritis (RA) is recognized as an autoimmune joint disease driven by T cell responses to self (or modified self or microbial mimic) antigens that trigger and aggravate the inflammatory condition. Newer treatments of RA employ monoclonal antibodies or recombinant receptors against cytokines or immune cell receptors as well as small-molecule Janus kinase (JAK) inhibitors to systemically ablate the cytokine or cellular responses that fuel inflammation. Unlike these treatments, a therapeutic vaccine, such as CEL-4000, helps balance adaptive immune homeostasis by promoting antigen-specific regulatory rather than inflammatory responses, and hence modulates the immunopathological course of RA. In this review, we discuss the current and proposed therapeutic products for RA, with an emphasis on antigen-specific therapeutic vaccine approaches to the treatment of the disease. As an example, we describe published results of the beneficial effects of CEL-4000 vaccine on animal models of RA. We also make a recommendation for the design of appropriate clinical studies for these newest therapeutic approaches, using the CEL-4000 vaccine as an example. Unlike vaccines that create or boost a new immune response, the clinical success of an immunomodulatory therapeutic vaccine for RA lies in its ability to redirect autoreactive pro-inflammatory memory T cells towards rebalancing the “runaway” immune/inflammatory responses that characterize the disease. Human trials of such a therapy will require alternative approaches in clinical trial design and implementation for determining safety, toxicity, and efficacy. These approaches include adaptive design (such as the Bayesian optimal design (BOIN), currently employed in oncological clinical studies), and the use of disease-related biomarkers as indicators of treatment success.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1334281/fullpeptide vaccineimmunotherapyrheumatoid arthritiscytokinesproteoglycan (PGaggrecan) |
| spellingShingle | Daniel H. Zimmerman Zoltan Szekanecz Adrienn Markovics Kenneth S. Rosenthal Roy E. Carambula Katalin Mikecz Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines Frontiers in Immunology peptide vaccine immunotherapy rheumatoid arthritis cytokines proteoglycan (PG aggrecan) |
| title | Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines |
| title_full | Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines |
| title_fullStr | Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines |
| title_full_unstemmed | Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines |
| title_short | Current status of immunological therapies for rheumatoid arthritis with a focus on antigen-specific therapeutic vaccines |
| title_sort | current status of immunological therapies for rheumatoid arthritis with a focus on antigen specific therapeutic vaccines |
| topic | peptide vaccine immunotherapy rheumatoid arthritis cytokines proteoglycan (PG aggrecan) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1334281/full |
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