8hxq
From Proteopedia
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/TNR17_HUMAN TNR17_HUMAN] Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.<ref>PMID:10903733</ref> <ref>PMID:10801128</ref> <ref>PMID:10973284</ref> | [https://www.uniprot.org/uniprot/TNR17_HUMAN TNR17_HUMAN] Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.<ref>PMID:10903733</ref> <ref>PMID:10801128</ref> <ref>PMID:10973284</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Ligand-induced receptor dimerization or oligomerization is a widespread mechanism for ensuring communication specificity, safeguarding receptor activation, and facilitating amplification of signal transduction across the cellular membrane. However, cell-surface antigen-induced multimerization (dubbed AIM herein) has not yet been consciously leveraged in chimeric antigen receptor (CAR) engineering for enriching T cell-based therapies. We co-developed ciltacabtagene autoleucel (cilta-cel), whose CAR incorporates two B-cell maturation antigen (BCMA)-targeted nanobodies in tandem, for treating multiple myeloma. Here we elucidated a structural and functional model in which BCMA-induced cilta-cel CAR multimerization amplifies myeloma-targeted T cell-mediated cytotoxicity. Crystallographic analysis of BCMA-nanobody complexes revealed atomic details of antigen-antibody hetero-multimerization whilst analytical ultracentrifugation and small-angle X-ray scattering characterized interdependent BCMA apposition and CAR juxtaposition in solution. BCMA-induced nanobody CAR multimerization enhanced cytotoxicity, alongside elevated immune synapse formation and cytotoxicity-mediating cytokine release, towards myeloma-derived cells. Our results provide a framework for contemplating the AIM approach in designing next-generation CARs. | ||
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| + | Antigen-induced chimeric antigen receptor multimerization amplifies on-tumor cytotoxicity.,Sun Y, Yang XN, Yang SS, Lyu YZ, Zhang B, Liu KW, Li N, Cui JC, Huang GX, Liu CL, Xu J, Mi JQ, Chen Z, Fan XH, Chen SJ, Chen S Signal Transduct Target Ther. 2023 Dec 8;8(1):445. doi: , 10.1038/s41392-023-01686-z. PMID:38062078<ref>PMID:38062078</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8hxq" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Nanobody1 in complex with human BCMA ECD
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