Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/115596
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dc.contributor.authorMärkl, Florian-
dc.contributor.authorAli Khan, Murtaza-
dc.contributor.authorPaschold, Lisa-
dc.contributor.authorZhang, Tianjiao-
dc.contributor.author[und viele weitere]-
dc.date.accessioned2024-04-09T06:15:27Z-
dc.date.available2024-04-09T06:15:27Z-
dc.date.issued2024-
dc.identifier.urihttps://opendata.uni-halle.de//handle/1981185920/117549-
dc.identifier.urihttp://dx.doi.org/10.25673/115596-
dc.description.abstractThe concept of precision cell therapy targeting tumor-specific mutations is appealing but requires surface-exposed neoepitopes, which is a rarity in cancer. B cell receptors (BCR) of mature lymphoid malignancies are exceptional in that they harbor tumor-specific-stereotyped sequences in the form of point mutations that drive self-engagement of the BCR and autologous signaling. Here, we use a BCR light chain neoepitope defined by a characteristic point mutation (IGLV3-21R110) for selective targeting of a poor-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. We develop murine and humanized CAR constructs expressed in T cells from healthy donors and CLL patients that eradicate IGLV3-21R110 expressing cell lines and primary CLL cells, but neither cells expressing the non-pathogenic IGLV3-21G110 light chain nor polyclonal healthy B cells. In vivo experiments confirm epitope-selective cytolysis in xenograft models in female mice using engrafted IGLV3-21R110 expressing cell lines or primary CLL cells. We further demonstrate in two humanized mouse models lack of cytotoxicity towards human B cells. These data provide the basis for advanced approaches of resistance-preventive and biomarker-guided cellular targeting of functionally relevant lymphoma driver mutations sparing normal B cells.eng
dc.language.isoeng-
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/-
dc.subject.ddc610-
dc.titleMutation-specific CAR T cells as precision therapy for IGLV3-21R110 expressing high-risk chronic lymphocytic leukemiaeng
dc.typeArticle-
local.versionTypepublishedVersion-
local.bibliographicCitation.journaltitleNature Communications-
local.bibliographicCitation.volume15-
local.bibliographicCitation.pagestart1-
local.bibliographicCitation.pageend14-
local.bibliographicCitation.publishernameNature Publishing Group UK-
local.bibliographicCitation.publisherplace[London]-
local.bibliographicCitation.doi10.1038/s41467-024-45378-w-
local.openaccesstrue-
dc.identifier.ppn188530885X-
cbs.publication.displayform2024-
local.bibliographicCitation.year2024-
cbs.sru.importDate2024-04-09T06:15:02Z-
local.bibliographicCitationEnthalten in Nature Communications - [London] : Nature Publishing Group UK, 2010-
local.accessrights.dnbfree-
Appears in Collections:Open Access Publikationen der MLU

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