Yousef Sara, Kovacsovics-Bankowski Magdalena, Salama Mohamed E, Bhardwaj Neelam, Steinbach Mary, Langemo Amanda, Kovacsovics Tibor, Marvin James, Binder Mascha, Panse Jens, Kröger Nicolaus, Luetkens Tim, Atanackovic Djordje
a Hematology and Hematologic Malignancies; University of Utah; Huntsman Cancer Institute ; Salt Lake City , UT , USA.
Hum Vaccin Immunother. 2015;11(7):1606-11. doi: 10.1080/21645515.2015.1046658.
Multiple Myeloma (MM) is a plasma cell (PC) malignancy, which despite significant therapeutic advances, is still considered incurable. This is due to the persistence of chemotherapy-resistant minimal residual disease in the patients' bone marrow (BM) after an effective induction therapy. Immunotherapies targeting surface molecules expressed on the bulk of tumor cells and the chemotherapy-resistant, myeloma-propagating cells could play a central role in this clinical setting. We recently described surface molecule CD229 as a potential therapeutic target for MM. In our current study we assessed the expression of CD229 on different PC subtypes and on cells with a myeloma-propagating phenotype in a total of 77 patients with PC dyscrasias independently at 2 different cancer centers. We found that CD229 was strongly and homogeneously overexpressed on the PC of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, MM, and PC leukemia. CD229 was particularly overexpressed on those PC showing an abnormal phenotype such as expression of CD56. Most importantly, CD229 was also highly expressed on those cells in the patients' BM displaying the phenotype of chemotherapy-resistant and myeloma-propagating cells. In conclusion, our combined findings suggest that immunotherapies targeting CD229 will not only be effective for the bulk of tumor cells but will also help to eradicate chemotherapy-resistant cells remaining in the patients' BM after induction treatment. Hopefully, the design of CD229-specific monoclonal antibodies or chimeric antigen receptor-transduced T cells will help to achieve prolonged remissions or even cures in MM patients.
多发性骨髓瘤（MM）是一种浆细胞（PC）恶性肿瘤，尽管在治疗方面取得了显著进展，但仍被认为无法治愈。这是因为在有效的诱导治疗后，患者骨髓（BM）中存在化疗耐药的微小残留病。针对大多数肿瘤细胞以及化疗耐药、骨髓瘤增殖细胞表面表达的分子的免疫疗法，可能在这种临床情况下发挥核心作用。我们最近将表面分子CD229描述为MM的潜在治疗靶点。在我们目前的研究中，我们在两个不同的癌症中心独立评估了77例浆细胞发育异常患者中不同PC亚型以及具有骨髓瘤增殖表型的细胞上CD229的表达。我们发现，CD229在意义未明的单克隆丙种球蛋白病（MGUS）、冒烟型骨髓瘤、MM和PC白血病患者的PC上强烈且均匀地过度表达。CD229在那些表现出异常表型（如CD56表达）的PC上尤其过度表达。最重要的是，CD229在患者BM中那些表现出化疗耐药和骨髓瘤增殖细胞表型的细胞上也高度表达。总之，我们的综合研究结果表明，靶向CD229的免疫疗法不仅对大多数肿瘤细胞有效，还将有助于根除诱导治疗后患者BM中残留的化疗耐药细胞。有望通过设计CD229特异性单克隆抗体或嵌合抗原受体转导的T细胞，帮助MM患者实现长期缓解甚至治愈。
