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Some studies have demonstrated that superantigens do not require intracellular processing and instated bind as intact proteins to the antigen\u2010binding groove of major histocompatibility complex II on antigen\u2010presenting cells, resulting in the activation of T cells with different T\u2010cell receptor V<jats:italic>\u03b2<\/jats:italic> and subsequent overstimulation. To combat superantigen\u2010mediated diseases, researchers have employed different approaches, such as antibodies and simulated peptides. However, due to the complex nature of superantigens, these approaches have not been entirely successful in achieving optimal therapeutic outcomes. CD28 interacts with members of the B7 molecule family to activate T cells. Its mimicking peptide has been suggested as a potential candidate to block superantigens, but it can lead to reduced T\u2010cell activity while increasing the host\u2019s infection risk. Thus, this review focuses on the use of drug delivery methods to accurately target and block superantigens, while reducing the adverse effects associated with CD28 mimic peptides. We believe that this method has the potential to provide an effective and safe therapeutic strategy for superantigen\u2010mediated diseases.<\/jats:p>","DOI":"10.1155\/2024\/2313062","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T22:20:09Z","timestamp":1705530009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Blocking Superantigen\u2010Mediated Diseases: Challenges and Future Trends"],"prefix":"10.1155","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4603-2572","authenticated-orcid":false,"given":"Pengbo","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4265-2990","authenticated-orcid":false,"given":"Zina","family":"Fredj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoguang","family":"Rong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9470-8143","authenticated-orcid":false,"given":"Sumin","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-7272","authenticated-orcid":false,"given":"Mohamad","family":"Sawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1289"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90980-X"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.941009"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1997.15.5.1994"},{"key":"e_1_2_10_5_2","first-page":"1903","article-title":"Superantigen-targeted therapy: phase I escalating repeat dose trial of the fusion protein PNU-214565 in patients with advanced gastrointestinal malignancies","volume":"4","author":"Alpaugh R. 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