Scholarlink

<p>Allogeneic chimeric antigen receptor (CAR) T cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) could be a therapeutic option for patients with relapsed or refractory, high-risk neuroblastoma (r/r HR-NB) whose tumors did not respond to autologous GD2-CART01 or who have profound lymphopenia. We present a case series of five children with HR-NB refractory to more than three different lines of therapy who received ALLO_GD2-CART01 in a hospital exemption setting. Four of them had previously received allogeneic hematopoietic stem cell transplantation. All patients experienced grade 2 or 3 cytokine release syndrome and one grade 2 neurotoxicity. Moderate acute graft-versus-host-disease occurred in four patients. ALLO_GD2-CART01 persisted for &gt;6 weeks. Post-treatment, two complete responses were achieved and one maintained; in addition, one partial response and one stable disease were observed. Comparing the transcriptomic profiles obtained by RNA sequencing analyses of drug products with patient-matched, peripheral blood ALLO_GD2-CART01 collected at expansion, we found upregulation of genes associated with T cell activation and migration. In addition, after infusion, transcriptomic signaling analysis showed enrichment of genes involved in response to decreased oxygen levels, humoral immune response, cell polarization and immune-synapse formation. In comparison to autologous CAR T cells, ALLO_GD2-CAR T cells were characterized by pathways associated with T cell proliferation, immune-synapse formation and cell chemotaxis. The safety and efficacy of ALLO_GD2-CART01 in children with r/r HR-NB deserve further investigation in a prospective trial.</p>

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

Donor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma

  • 期刊论文

  • 发表日期：

    2025年1月15日

查看全文
  • Concetta Quintarelli,
  • Francesca Del Bufalo,
  • Maria Antonietta De Ioris,
  • Marika Guercio,
  • Mattia Algeri,
  • Daria Pagliara,
  • Domenico Alessandro Silvestris,
  • Matteo Di Nardo,
  • Matilde Sinibaldi,
  • Stefano Di Cecca,
  • Laura Iaffaldano,
  • Simona Manni,
  • Valentina Fustaino,
  • Maria Carmen Garganese,
  • Giovanna Stefania Colafati,
  • Valentina Bertaina,
  • Marco Becilli,
  • Angela Mastronuzzi,
  • Francesco Fabozzi,
  • Monica Gunetti,
  • Stefano Iacovelli,
  • Rossana Bugianesi,
  • Stefania Macchia,
  • Giuseppina Li Pira,
  • Maria Giuseppina Cefalo,
  • Giovanna Leone,
  • Giada Del Baldo,
  • Biagio De Angelis,
  • Franco Locatelli

摘要

Allogeneic chimeric antigen receptor (CAR) T cells targeting disialoganglioside-GD2 (ALLO_GD2-CART01) could be a therapeutic option for patients with relapsed or refractory, high-risk neuroblastoma (r/r HR-NB) whose tumors did not respond to autologous GD2-CART01 or who have profound lymphopenia. We present a case series of five children with HR-NB refractory to more than three different lines of therapy who received ALLO_GD2-CART01 in a hospital exemption setting. Four of them had previously received allogeneic hematopoietic stem cell transplantation. All patients experienced grade 2 or 3 cytokine release syndrome and one grade 2 neurotoxicity. Moderate acute graft-versus-host-disease occurred in four patients. ALLO_GD2-CART01 persisted for >6 weeks. Post-treatment, two complete responses were achieved and one maintained; in addition, one partial response and one stable disease were observed. Comparing the transcriptomic profiles obtained by RNA sequencing analyses of drug products with patient-matched, peripheral blood ALLO_GD2-CART01 collected at expansion, we found upregulation of genes associated with T cell activation and migration. In addition, after infusion, transcriptomic signaling analysis showed enrichment of genes involved in response to decreased oxygen levels, humoral immune response, cell polarization and immune-synapse formation. In comparison to autologous CAR T cells, ALLO_GD2-CAR T cells were characterized by pathways associated with T cell proliferation, immune-synapse formation and cell chemotaxis. The safety and efficacy of ALLO_GD2-CART01 in children with r/r HR-NB deserve further investigation in a prospective trial.