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Activation of the adaptive immune system involving T cells, B cells, and macrophages along with microvasculopathy is considered early events in disease pathogenesis. Today, immunosuppressives, including anti-B cell biologics, form the foundation of SSc treatment; however, significant therapeutic needs remain unmet. Autologous chimeric antigen receptor (CAR)-T cells, targeting B cell CD19 and inducing deep depletion of B cells, were tested in a few patients with SSc, leading to improvement of skin score, arthritis, digital ulcers, and inflammatory changes in heart and lungs. However, regression of lung fibrosis remains a major therapeutic challenge. In addition, autologous CAR-T cells are a personalized treatment that requires a specialized setting, is not readily available, is costly, and is associated with serious adverse effects, including cytokine release syndrome, neurotoxicity, and increased risk of infection. New developments in CAR T cell technology, including off-the-shelf allogeneic CAR T cells, bispecific CAR-T cells, and CAR NK cells, are being tested in patients with progressive refractory SSc.<\/jats:p>\n                  <jats:p>\n                    <jats:table-wrap>\n                      <jats:table>\n                        <jats:tbody>\n                          <jats:tr>\n                            <jats:td align=\"left\" colspan=\"2\">\n                              Key Points\u2022\n                              <jats:italic>There is unmet therapeutic need for systemic sclerosis(SSc).<\/jats:italic>\n                              \u2022\n                              <jats:italic>Autologous CAR-T cells targeting CD19 showed efficacy in SSc, but are a personalized, expensive and not readily available treatment.<\/jats:italic>\n                              \u2022\n                              <jats:italic>Off-the-shelf allogeneic CAR-T cells and CAR-NK cells are being evaluated in SSc.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                        <\/jats:tbody>\n                      <\/jats:table>\n                    <\/jats:table-wrap>\n                  <\/jats:p>","DOI":"10.1007\/s10067-025-07554-1","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T13:51:40Z","timestamp":1751637100000},"page":"651-656","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["CAR-T cells in systemic sclerosis"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-3314","authenticated-orcid":false,"given":"Lazaros I.","family":"Sakkas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4174-6576","authenticated-orcid":false,"given":"Chistina","family":"Katsiari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1788-0310","authenticated-orcid":false,"given":"Vasiliki","family":"Syrmou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8602-0958","authenticated-orcid":false,"given":"Ian C.","family":"Chikanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"7554_CR1","doi-asserted-by":"crossref","unstructured":"Volkman ER, Andreasson K, Smith V (2023). 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