Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy.
Glycoengineering of NK Cells with Glycan Ligands of CD22 and Selectins for B-Cell Lymphoma Therapy.
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DOI：
10.1002/anie.202005934
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发表时间：
2021-02-15
期刊：
影响因子：
--
通讯作者：
Wu P
中科院分区：
文献类型：
--
作者：
Hong S;Yu C;Wang P;Shi Y;Cao W;Cheng B;Chapla DG;Ma Y;Li J;Rodrigues E;Narimatsu Y;Yates JR 3rd;Chen X;Clausen H;Moremen KW;Macauley MS;Paulson JC;Wu P
CD22是唾液酸结合蛋白Siglec家族的一员，在B细胞上表达受限。针对B淋巴瘤和白血病细胞的CD22或CD20的抗体药物在治疗这些恶性肿瘤方面表现出临床疗效，但也会攻击正常的B细胞导致免疫缺陷。在这里，我们报道了一种化学酶糖萼编辑策略，将高亲和力和特异性CD22配体引入NK-92MI和细胞因子诱导的杀伤细胞，以实现肿瘤特异性CD22靶向。这些cd22配体修饰的细胞在体外表现出明显增强的肿瘤细胞结合和杀伤能力，而不损害健康的B细胞。为了在体内有效杀伤淋巴瘤细胞，我们进一步用e -选择素配体sialyl Lewis X功能化CD22配体修饰的NK-92MI细胞，以促进向骨髓的运输。在异种移植模型中，双功能细胞有效抑制了B淋巴瘤。我们的研究结果表明，用CD22和选择素修饰的聚糖配体修饰的自然杀伤细胞分别促进了B淋巴瘤细胞的靶向杀伤和癌细胞所在部位的运输。探索外源性糖转移酶辅助的化学酶方法来编辑活免疫细胞表面聚糖的结构，反过来，能够原位生成癌症特异性病理标记的配体。在这里，我们报道了cd22特异性配体和唾液Lewis X在NK细胞（NK- 92mi或CIK细胞）上的产生，以有效地靶向和根除b淋巴瘤。
CD22, a member of Siglec family of sialic acid binding proteins, has restricted expression on B cells. Antibody-based agents targeting CD22 or CD20 on B lymphoma and leukemia cells exhibit clinical efficacy for treating these malignancies, but also attack normal B cells leading to immune deficiency. Here, we report a chemoenzymatic glycocalyx editing strategy to introduce high-affinity and specific CD22 ligands onto NK-92MI and cytokine-induced killer cells to achieve tumor-specific CD22 targeting. These CD22-ligand modified cells exhibited significantly enhanced tumor cell binding and killing in vitro without harming healthy B cells. For effective lymphoma cell killing in vivo we further functionalized CD22 ligand-modified NK-92MI cells with the E-selectin ligand sialyl Lewis X to promote trafficking to bone marrow. The dual-functionalized cells resulted in the efficient suppression of B lymphoma in a xenograft model. Our results suggest that nature killer cells modified with glycan ligands to CD22 and selectins promote both targeted killing of B lymphoma cells and improved trafficking to sites where the cancer cells reside, respectively. Exploring the exogenous glycotransferase-assisted chemoenzymatic approaches to edit the structure of live immune cell-surface glycans, in turn, enables in situ generation of the ligands for cancer specific pathology-markers. Here we reported the creation of CD22-specific ligands and sialyl Lewis X on NK cells (NK-92MI or CIK cells) to target and eradicate B-lymphoma efficiently.
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DOI：
10.1007/s00262-018-2247-4
发表时间：
2019-01
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Lee JH;Lee JH;Lim YS;Yeon JE;Song TJ;Yu SJ;Gwak GY;Kim KM;Kim YJ;Lee JW;Yoon JH
通讯作者：
Yoon JH
影响因子：
56.9
作者：
PHILLIPS, ML;NUDELMAN, E;PAULSON, JC
通讯作者：
PAULSON, JC
影响因子：
7.3
作者：
Klingemann H;Boissel L;Toneguzzo F
通讯作者：
Toneguzzo F
影响因子：
15
作者：
Nycholat CM;Peng W;McBride R;Antonopoulos A;de Vries RP;Polonskaya Z;Finn MG;Dell A;Haslam SM;Paulson JC
通讯作者：
Paulson JC
影响因子：
16.6
作者：
Kelm, Sorge;Madge, Paul;Haselhorst, Thomas
通讯作者：
Haselhorst, Thomas