ScholarLink (思领科)
错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Treatment of secondary CNS lymphoma using CD19-targeted chimeric antigen receptor (CAR) T cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2024年2月13日

查看全文
  • Kathryn Kline,
  • Tim Luetkens,
  • Rima Koka,
  • Michael E. Kallen,
  • Wengen Chen,
  • Haroon Ahmad,
  • Destiny Omili,
  • Thierry Iraguha,
  • Etse Gebru,
  • Xiaoxuan Fan,
  • Alexis Miller,
  • Nishanthini Dishanthan,
  • Jillian M. Baker,
  • Kenneth A. Dietze,
  • Kim G. Hankey,
  • Jean A. Yared,
  • Nancy M. Hardy,
  • Aaron P. Rapoport,
  • Saurabh Dahiya,
  • Djordje Atanackovic

摘要

Background

Aggressive B cell lymphoma with secondary central nervous system (CNS) involvement (SCNSL) carries a dismal prognosis. Chimeric antigen receptor (CAR) T cells (CAR-T) targeting CD19 have revolutionized the treatment for B cell lymphomas; however, only single cases with CNS manifestations successfully treated with CD19 CAR-T have been reported.

Methods

We prospectively enrolled 4 patients with SCNSL into our study to assess clinical responses and monitor T cell immunity.

Results

Two of four SNCSL patients responded to the CD19-targeted CAR-T. Only one patient showed a substantial expansion of peripheral (PB) CAR-T cells with an almost 100-fold increase within the first week after CAR-T. The same patient also showed marked neurotoxicity and progression of the SNCSL despite continuous surface expression of CD19 on the lymphoma cells and an accumulation of CD4+ central memory-type CAR-T cells in the CNS. Our studies indicate that the local production of chemokine IP-10, possibly through its receptor CXCR3 expressed on our patient’s CAR-T, could potentially have mediated the local accumulation of functionally suboptimal anti-tumor T cells.

Conclusions

Our results demonstrate expansion and homing of CAR-T cells into the CNS in SNCSL patients. Local production of chemokines such as IP-10 may support CNS infiltration by CAR-T cells but also carry the potential of amplifying local toxicity. Future studies investigating numbers, phenotype, and function of CAR-T in the different body compartments of SNSCL patients receiving CAR-T will help to improve local delivery of “fit” and highly tumor-reactive CAR-T with low off-target reactivity into the CNS.