CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Rapid anti-myeloma activity by T cells expressing an anti-BCMA CAR with a human heavy-chain-only antigen-binding domain.
Rapid anti-myeloma activity by T cells expressing an anti-BCMA CAR with a human heavy-chain-only antigen-binding domain.
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多发性骨髓瘤（MM）是一种罕见的、难以治愈的浆细胞恶性肿瘤。MM表达B细胞成熟抗原（BCMA）。我们开发了一种全人源抗BCMA嵌合抗原受体（CAR），其包含仅重链的抗原识别结构域、4-1BB结构域和CD3ζ结构域。该CAR被命名为FHVH33-CD8BBZ。
我们开展了表达FHVH33-CD8BBZ的T细胞（FHVH-T）的首次人体临床试验。25例复发MM患者接受了治疗。严格完全缓解率（sCR）为52%。中位无进展生存期（PFS）为78周。在24例可评估患者中，6例（25%）的最大细胞因子释放综合征（CRS）分级为3级；无患者出现高于3级的CRS。大多数抗MM活性发生在FHVH-T输注后2-4周内，表现为快速变化的MM标志物血清游离轻链、尿轻链和骨髓浆细胞的下降。血液CAR+细胞水平在MM清除发生期间达到峰值，即FHVH-T输注后7至15天。输注CD4+ FHVH-T上C-C趋化因子受体7型（CCR7）的表达与血液FHVH-T峰值水平相关。单细胞RNA测序显示输注后FHVH-T向更分化状态转变。在12例接受评估的患者中，4例检测到抗CAR抗体反应。FHVH-T具有强大、快速且持久的抗MM活性。
Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA).
We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ.
We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater than grade 3. Most anti-MM activity occurred within 2-4 weeks of FHVH-T infusion as shown by decreases in the rapidly changing MM markers serum free light chains, urine light chains, and bone marrow plasma cells.
Blood CAR + cell levels peaked during the time that MM elimination was occurring, between 7 and 15 days after FHVH-T infusion. C-C chemokine receptor type 7 (CCR7) expression on infusion CD4 + FHVH-T correlated with peak blood FHVH-T levels. Single-cell RNA sequencing revealed a shift toward more differentiated FHVH-T after infusion. Anti-CAR antibody responses were detected in 4 of 12 patients assessed. FHVH-T has powerful, rapid, and durable anti-MM activity.
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →
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