Multiple Myeloma Program & Cancer Immunotherapy, Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, 84112, USA.
Nat Commun. 2020 Feb 7;11(1):798. doi: 10.1038/s41467-020-14619-z.
Multiple myeloma (MM) is a plasma cell malignancy and most patients eventually succumb to the disease. Chimeric antigen receptor (CAR) T cells targeting B-Cell Maturation Antigen (BCMA) on MM cells have shown high-response rates, but limited durability. CD229/LY9 is a cell surface receptor present on B and T lymphocytes that is universally and strongly expressed on MM plasma cells. Here, we develop CD229 CAR T cells that are highly active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells. We do not observe fratricide during CD229 CAR T cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229 T cells, they spare functional CD229 T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM.
多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，大多数患者最终会死于该疾病。针对 MM 细胞上的 B 细胞成熟抗原（BCMA）的嵌合抗原受体（CAR）T 细胞已显示出高应答率，但持久性有限。CD229/LY9 是一种存在于 B 和 T 淋巴细胞表面的受体，在 MM 浆细胞上普遍且强烈表达。在这里，我们开发了 CD229 CAR T 细胞，这些细胞在体外和体内对 MM 浆细胞、记忆 B 细胞和 MM 传播细胞具有高度活性。在 CD229 CAR T 细胞的生产过程中，我们没有观察到自相残杀现象，因为 CD229 在 T 细胞激活过程中下调。此外，虽然 CD229 CAR T 细胞靶向正常的 CD229 T 细胞，但它们能保留功能正常的 CD229 T 细胞。这些发现表明，CD229 CAR T 细胞可能是 MM 患者的有效治疗方法。
