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Its high B cell lineage specificity, rapid internalization capacity, and signal attenuation mediated by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) render it an ideal therapeutic target for B cell-related pathologies. In recent years, CD22-targeted therapeutic strategies have demonstrated significant clinical breakthroughs in the treatment of hematological malignancies and autoimmune diseases. These strategies encompass immunotoxins, radioimmunoconjugates, antibody\u2013drug conjugates (ADCs), bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy. Notably, while monotherapies have achieved high response rates, dual-targeting approaches (e.g., CD19\/CD22 CAR-T) have further mitigated the risk of antigen escape and profoundly enhanced long-term durable efficacy. This review systematically summarizes the molecular mechanisms of CD22 and the latest clinical advancements in its targeted therapies. Furthermore, we highlight the promising translational potential of CD22-targeted strategies\u2014particularly CAR-T cell therapy\u2014from oncology to the management of autoimmune disorders, outlining future research priorities within this rapidly evolving field.<\/jats:p>","DOI":"10.3390\/ijms27125406","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T09:06:52Z","timestamp":1781600812000},"page":"5406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD22 as a Target for Hematological Malignancies and Autoimmune Diseases"],"prefix":"10.3390","volume":"27","author":[{"given":"Xin","family":"Chen","sequence":"first","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Zhang","sequence":"additional","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sizhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China"},{"name":"Department of Public Health Dunedin, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2779-0642","authenticated-orcid":false,"given":"Chaojun","family":"Yan","sequence":"additional","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-3843","authenticated-orcid":false,"given":"Cefan","family":"Zhou","sequence":"additional","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5524-4518","authenticated-orcid":false,"given":"Jingfeng","family":"Tang","sequence":"additional","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0005-328X","authenticated-orcid":false,"given":"Rachael Mira","family":"McLean","sequence":"additional","affiliation":[{"name":"Department of Public Health Dunedin, University of Otago, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"National \u201c111\u201d Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Hubei Key Laboratory of Industrial Microbiology, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e20200851","DOI":"10.1084\/jem.20200851","article-title":"B cells and cancer: To B or not to B?","volume":"218","author":"Fridman","year":"2021","journal-title":"J. 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