Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22.
Structural details of monoclonal antibody m971 recognition of the membrane-proximal domain of CD22.
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DOI：
10.1016/j.jbc.2021.100966
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Julien JP
中科院分区：
文献类型：
--
作者：
Ereño-Orbea J;Liu X;Sicard T;Kucharska I;Li W;Borovsky D;Cui H;Feng Y;Dimitrov DS;Julien JP
Cluster of differentiation-22 (CD22) belongs to the sialic acid–binding immunoglobulin (Ig)-like lectin family of receptors that is expressed on the surface of B cells. It has been classified as an inhibitory coreceptor for the B-cell receptor because of its function in establishing a baseline level of B-cell inhibition. The restricted expression of CD22 on B cells and its inhibitory function make it an attractive target for B-cell depletion in cases of B-cell malignancies. Genetically modified T cells with chimeric antigen receptors (CARs) derived from the m971 antibody have shown promise when used as an immunotherapeutic agent against B-cell acute lymphoblastic leukemia. A key aspect of the efficacy of this CAR-T was its ability to target a membrane-proximal epitope on the CD22 extracellular domain; however, the molecular details of m971 recognition of CD22 have thus far remained elusive. Here, we report the crystal structure of the m971 fragment antigen-binding in complex with the two most membrane-proximal Ig-like domains of CD22 (CD22d6–d7). The m971 epitope on CD22 resides at the most proximal Ig domain (d7) to the membrane, and the antibody paratope contains electrostatic surfaces compatible with interactions with phospholipid head groups. Together, our data identify molecular details underlying the successful transformation of an antibody epitope on CD22 into an effective CAR immunotherapeutic target.
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影响因子：
17.1
作者：
Brentjens RJ;Davila ML;Riviere I;Park J;Wang X;Cowell LG;Bartido S;Stefanski J;Taylor C;Olszewska M;Borquez-Ojeda O;Qu J;Wasielewska T;He Q;Bernal Y;Rijo IV;Hedvat C;Kobos R;Curran K;Steinherz P;Jurcic J;Rosenblat T;Maslak P;Frattini M;Sadelain M
通讯作者：
Sadelain M
影响因子：
20.3
作者：
Gardner, Rebecca;Wu, David;Turtle, Cameron J.
通讯作者：
Turtle, Cameron J.
影响因子：
5.6
作者：
Ereno-Orbea, June;Sicard, Taylor;Julien, Jean-Philippe
通讯作者：
Julien, Jean-Philippe
影响因子：
4.6
作者：
Park S;Shevlin E;Vedvyas Y;Zaman M;Park S;Hsu YS;Min IM;Jin MM
通讯作者：
Jin MM
DOI：
10.1073/pnas.1716266115
发表时间：
2018-02-27
影响因子：
11.1
作者：
Davenport AJ;Cross RS;Watson KA;Liao Y;Shi W;Prince HM;Beavis PA;Trapani JA;Kershaw MH;Ritchie DS;Darcy PK;Neeson PJ;Jenkins MR
通讯作者：
Jenkins MR