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Mol. Life Sci."],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The\u00a0link between cancer and aberrant glycosylation has recently become evident. Glycans and their altered forms, known as tumour-associated carbohydrate antigens (TACAs), are diverse, complex and difficult to target therapeutically. Lectins are naturally occurring glycan-binding proteins \u00a0that offer a unique opportunity to recognise TACAs. T cells expressing chimeric antigen receptors (CARs) have proven to be a successful immunotherapy against leukaemias, but so far have shown limited success in solid tumours. We developed a panel of lectin-CARs that recognise the glycosphingolipid globotriaosylceramide (Gb3), which is overexpressed in various cancers, such as Burkitt's lymphoma, colorectal, breast and pancreatic. We have selected the following lectins: Shiga toxin's B-subunit from <jats:italic>Shigella dysenteriae<\/jats:italic>, LecA from <jats:italic>Pseudomonas aeruginosa<\/jats:italic>, and the engineered lectin Mitsuba from <jats:italic>Mytilus galloprovincialis<\/jats:italic> as antigen-binding domains and fused them to a well-known second-generation CAR. The Gb3-binding lectin-CARs have demonstrated target-specific cytotoxicity against Burkitt's lymphoma-derived cell lines as well as solid tumour cells from colorectal and triple-negative breast cancer. Our findings reveal the big potential of lectin-based CARs as therapeutical applications to target Gb3 and other TACAs expressed in haematological malignancies and solid tumours.<\/jats:p>","DOI":"10.1007\/s00018-022-04524-7","type":"journal-article","created":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T19:02:41Z","timestamp":1663009361000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Novel lectin-based chimeric antigen receptors target Gb3-positive tumour cells"],"prefix":"10.1007","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6267-2855","authenticated-orcid":false,"given":"Ana Valeria","family":"Mel\u00e9ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1764-115X","authenticated-orcid":false,"given":"Rub\u00ed M.-H.","family":"Velasco C\u00e1rdenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-1781","authenticated-orcid":false,"given":"Simon","family":"Lagies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Strietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-1916","authenticated-orcid":false,"given":"Lina","family":"Siukstaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1949-0938","authenticated-orcid":false,"given":"Oliver S.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Tomisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4340-4446","authenticated-orcid":false,"given":"Wilfried","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kammerer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-246X","authenticated-orcid":false,"given":"Winfried","family":"R\u00f6mer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8211-5538","authenticated-orcid":false,"given":"Susana","family":"Minguet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"4524_CR1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-281931","author":"JN Kochenderfer","year":"2010","unstructured":"Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA, Maric I, Raffeld M, Nathan DAN, Lanier BJ, Morgan RA, Rosenberg SA (2010) Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. 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