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Nanobody based dual specific CARs

Stijn De Munter (UGent) , Joline Ingels (UGent) , Glenn Goetgeluk (UGent) , Sarah Bonte (UGent) , Melissa Pille (UGent) , Karin Weening (UGent) , Tessa Kerre (UGent) , Hinrich Abken and Bart Vandekerckhove (UGent)
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Abstract
Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.
Keywords
CAR T cell, nanobody, antigen escape, CHIMERIC ANTIGEN RECEPTORS, SINGLE-DOMAIN ANTIBODIES, MODIFIED T-CELLS, ACUTE LYMPHOBLASTIC-LEUKEMIA, B-CELL, ANTITUMOR-ACTIVITY, IMMUNE ESCAPE, THERAPY, RESISTANCE, IMMUNOTHERAPY

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MLA
De Munter, Stijn et al. “Nanobody Based Dual Specific CARs.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 19.2 (2018): n. pag. Print.
APA
De Munter, S., Ingels, J., Goetgeluk, G., Bonte, S., Pille, M., Weening, K., Kerre, T., et al. (2018). Nanobody based dual specific CARs. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 19(2).
Chicago author-date
De Munter, Stijn, Joline Ingels, Glenn Goetgeluk, Sarah Bonte, Melissa Pille, Karin Weening, Tessa Kerre, Hinrich Abken, and Bart Vandekerckhove. 2018. “Nanobody Based Dual Specific CARs.” International Journal of Molecular Sciences 19 (2).
Chicago author-date (all authors)
De Munter, Stijn, Joline Ingels, Glenn Goetgeluk, Sarah Bonte, Melissa Pille, Karin Weening, Tessa Kerre, Hinrich Abken, and Bart Vandekerckhove. 2018. “Nanobody Based Dual Specific CARs.” International Journal of Molecular Sciences 19 (2).
Vancouver
1.
De Munter S, Ingels J, Goetgeluk G, Bonte S, Pille M, Weening K, et al. Nanobody based dual specific CARs. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2018;19(2).
IEEE
[1]
S. De Munter et al., “Nanobody based dual specific CARs,” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 19, no. 2, 2018.
@article{8548337,
  abstract     = {Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B cell leukemias and lymphomas. However, targeting a single antigen may not be sufficient, and relapse due to the emergence of antigen negative leukemic cells may occur. A potential strategy to counter the outgrowth of antigen escape variants is to broaden the specificity of the CAR by incorporation of multiple antigen recognition domains in tandem. As a proof of concept, we here describe a bispecific CAR in which the single chain variable fragment (scFv) is replaced by a tandem of two single-antibody domains or nanobodies (nanoCAR). High membrane nanoCAR expression levels are observed in retrovirally transduced T cells. NanoCARs specific for CD20 and HER2 induce T cell activation, cytokine production and tumor lysis upon incubation with transgenic Jurkat cells expressing either antigen or both antigens simultaneously. The use of nanobody technology allows for the production of compact CARs with dual specificity and predefined affinity.},
  articleno    = {403},
  author       = {De Munter, Stijn and Ingels, Joline and Goetgeluk, Glenn and Bonte, Sarah and Pille, Melissa and Weening, Karin and Kerre, Tessa and Abken, Hinrich and Vandekerckhove, Bart},
  issn         = {1422-0067},
  journal      = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
  keywords     = {CAR T cell,nanobody,antigen escape,CHIMERIC ANTIGEN RECEPTORS,SINGLE-DOMAIN ANTIBODIES,MODIFIED T-CELLS,ACUTE LYMPHOBLASTIC-LEUKEMIA,B-CELL,ANTITUMOR-ACTIVITY,IMMUNE ESCAPE,THERAPY,RESISTANCE,IMMUNOTHERAPY},
  language     = {eng},
  number       = {2},
  pages        = {11},
  title        = {Nanobody based dual specific CARs},
  url          = {http://dx.doi.org/10.3390/ijms19020403},
  volume       = {19},
  year         = {2018},
}

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