000K  utf8
1100  $c2021
1500  eng
2050  urn:nbn:de:gbv:8:3-2021-00779-2
2051  10.3389/fcell.2021.698503
3000  Lobastova, Liudmila
3010  Babatz, Felix
3010  de Oliveira, Thais Dolzany
3010  Dürkop, Horst
3010  Hallek, Michael
3010  Hansen, Hinrich P
3010  Janssen, Ottmar
3010  Lettau, Marcus
3010  Nguyen, Phuong-Hien
3010  Paes Leme, Adriana F
3010  Pauletti, Bianca Alves
3010  Schauss, Astrid C
4000  CD30-Positive Extracellular Vesicles Enable the Targeting of CD30-Negative DLBCL Cells by the CD30 Antibody-Drug Conjugate Brentuximab Vedotin  [Lobastova, Liudmila]
4209  CD30, a member of the TNF receptor superfamily, is selectively expressed on a subset of activated lymphocytes and on malignant cells of certain lymphomas, such as classical Hodgkin Lymphoma (cHL), where it activates critical bystander cells in the tumor microenvironment. Therefore, it is not surprising that the CD30 antibody-drug conjugate Brentuximab Vedotin (BV) represents a powerful, FDA-approved treatment option for CD30+ hematological malignancies. However, BV also exerts a strong anti-cancer efficacy in many cases of diffuse large B cell lymphoma (DLBCL) with poor CD30 expression, even when lacking detectable CD30+ tumor cells. The mechanism remains enigmatic. Because CD30 is released on extracellular vesicles (EVs) from both, malignant and activated lymphocytes, we studied whether EV-associated CD30 might end up in CD30- tumor cells to provide binding sites for BV. Notably, CD30+ EVs bind to various DLBCL cell lines as well as to the FITC-labeled variant of the antibody-drug conjugate BV, thus potentially conferring the BV binding also to CD30- cells. Confocal microscopy and imaging cytometry studies revealed that BV binding and uptake depend on CD30+ EVs. Since BV is only toxic toward CD30- DLBCL cells when CD30+ EVs support its uptake, we conclude that EVs not only communicate within the tumor microenvironment but also influence cancer treatment. Ultimately, the CD30-based BV not only targets CD30+ tumor cell but also CD30- DLBCL cells in the presence of CD30+ EVs. Our study thus provides a feasible explanation for the clinical impact of BV in CD30- DLBCL and warrants confirming studies in animal models.
4950  https://doi.org/10.3389/fcell.2021.698503$xR$3Volltext$534
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2021-00779-2$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/macau_mods_00002072
5051  610
5550  Antibody-drug Conjugate
5550  Cellular Crosstalk
5550  Extracellular Vesicle
5550  immune therapy
5550  Tumor Microenvironment