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The approval of BCR::ABL1 tyrosine kinase inhibitors (TKI) such as imatinib, dasatinib, nilotinib and ponatinib marked a milestone in targeted therapy only for a subset of patients carrying the translocation t(9;22)(q34;q11). Immunotherapy with the bispecific antibody (bsAb) blinatumomab targeting CD19xCD3 revolutionized treatment of all B-ALL cases. The combination of both TKI and bsAb, so-called \u201cdual targeting\u201d, is currently under clinical investigation, although TKI might influence T cell effects.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We here investigated the combination of different TKI and blinatumomab in BCR::ABL1<jats:sup>+<\/jats:sup> and BCR::ABL1<jats:sup>\u2212<\/jats:sup> B-ALL cell lines and primary samples regarding T cell proliferation, differentiation, cytokine release and killing of tumor cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In vitro analysis revealed profound reduction of T cell proliferation, differentiation, cytokine release and killing of tumor cells upon application of BCR::ABL1 TKI with blinatumomab. Inhibition was more pronounced with dasatinib and ponatinib compared to nilotinib and imatinib. T cell signalling after CD3 stimulation was impaired by TKI mirrored by inhibition of LCK phosphorylation. This known off-target effect might influence the efficacy of bsAb therapy when combined with BCR::ABL1 TKI.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In conclusion, we propose that nilotinib and imatinib might also be suitable substances for combination with blinatumomab and suggest evaluation in clinical trials.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00432-022-04039-5","type":"journal-article","created":{"date-parts":[[2022,5,13]],"date-time":"2022-05-13T04:03:49Z","timestamp":1652414629000},"page":"2759-2771","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["BCR::ABL1 tyrosine kinase inhibitors hamper the therapeutic efficacy of blinatumomab in vitro"],"prefix":"10.1007","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1632-0167","authenticated-orcid":false,"given":"Joseph","family":"Kauer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2920-3894","authenticated-orcid":false,"given":"Melanie","family":"M\u00e4rklin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pfl\u00fcgler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8023-4258","authenticated-orcid":false,"given":"Sebastian","family":"H\u00f6rner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-9399","authenticated-orcid":false,"given":"Clemens","family":"Hinterleitner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Tandler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2831-2829","authenticated-orcid":false,"given":"Gundram","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-1847","authenticated-orcid":false,"given":"Helmut R.","family":"Salih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-8620","authenticated-orcid":false,"given":"Jonas S.","family":"Heitmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,13]]},"reference":[{"issue":"8","key":"4039_CR1","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1634\/stemcells.2005-0069","volume":"23","author":"S Appel","year":"2005","unstructured":"Appel S, Balabanov S, Brummendorf TH, Brossart P (2005) Effects of imatinib on normal hematopoiesis and immune activation. 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