Bridging Allogeneic Hematopoietic Stem Cell Transplantation or Not After CD19 CAR - T (S1904) Cell Therapy for R/r B-cell Acute Lymphoblastic Leukemia, a Prospective, Open, Multicenter, Randomized, Control Study (COMPLETE Study)

Traditional salvage chemotherapy has low efficacy and poor long-term prognosis for relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Targeted CD19 CAR-T cell immunotherapy is an effective means of treating R/R B-ALL. Several clinical studies have shown that its remission rate for R/R B-ALL can reach 68-93%. However, long-term follow-up found that the remission time after CD19 CAR-T treatment is short and the relapse rate is high. Therefore, how to ensure the long-term survival of R/R B-ALL patients after remission by CAR-T therapy is an urgent problem to be solved. Some studies have shown that timely bridging allo-HSCT after CAR-T treatment can overcome the risk of relapse and further improve the long-term survival of patients. However, there is currently no randomized controlled study on whether to bridge transplantation after CAR-T. The purpose of this study is to evaluate the efficacy and safety of S1904 in the treatment of relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia with or without bridging to allogeneic hematopoietic stem cell transplantation after remission.

开始日期2024-10-01

申办/合作机构

北京大学人民医院

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100 项与 CD19 CAR - T Cell(Peking University People's Hospital) 相关的临床结果

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100 项与 CD19 CAR - T Cell(Peking University People's Hospital) 相关的转化医学

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100 项与 CD19 CAR - T Cell(Peking University People's Hospital) 相关的专利（医药）

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项与 CD19 CAR - T Cell(Peking University People's Hospital) 相关的文献（医药）

Experimental hematology & oncology

A novel CAR-T cell product targeting CD74 is an effective therapeutic approach in preclinical mantle cell lymphoma models

Article

作者: Pray, Betsy ; Hanel, Walter ; Sharma, Archisha ; Yang, Yiping ; Sorathia, Kinnari ; Sloan, Shelby L ; Muthusamy, Natarajan ; Zhang, Xiaoli ; Chan, Wing Keung ; Alinari, Lapo ; Bian, Zehua ; Vasu, Sumithira ; Abusaleh, Kaled ; Hout, Ian ; Williams, Jessica ; de Lima, Marcos ; Yasin, Aneeq ; Nishat, Shamama ; Denlinger, Nathan ; Baiocchi, Robert

Abstract:

Background:

Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma subtype which remains incurable despite multimodal approach including chemoimmunotherapy followed by stem cell transplant, targeted approaches such as the BTK inhibitor ibrutinib, and CD19 chimeric antigen receptor (CAR) T cells. CD74 is a nonpolymorphic type II integral membrane glycoprotein identified as an MHC class II chaperone and a receptor for macrophage migration inhibitory factor. Our group previously reported on CD74's abundant expression in MCL and its ability to increase via pharmacological inhibition of autophagosomal degradation. Milatuzumab, a fully humanized anti-CD74 monoclonal antibody, demonstrated significant activity in preclinical lymphoma models but failed to provide meaningful benefits in clinical trials mainly due to its short half-life. We hypothesized that targeting CD74 using a CAR-T cell would provide potent and durable anti-MCL activity.

Methods:

We engineered a second generation anti-CD74 CAR with 4-1BB and CD3ζ signaling domains (74bbz). Through in silico and rational mutagenesis on the scFV domain, the 74bbz CAR was functionally optimized for superior antigen binding affinity, proliferative signaling, and cytotoxic activity against MCL cells in vitro and in vivo.

Results:

Functionally optimized 74bbz CAR-T cells (clone 42105) induced significant killing of MCL cell lines, and primary MCL patient samples including one relapse after commercial CD19 CAR-T cell therapy with direct correlation between antigen density and cytotoxicity. It significantly prolonged the survival of an animal model established in NOD-SCIDγc−/− (NSG) mice engrafted with a human MCL cell line Mino subcutaneously compared to controls. Finally, while CD74 is also expressed on normal immune cell subsets, treatment with 74bbz CAR-T cells resulted in minimal cytotoxicity against these cells both in vitro and in vivo.

Conclusions:

Targeting CD74 with 74bbz CAR-T cells represents a new cell therapy to provide a potent and durable and anti-MCL activity.

Immunotherapy

A lesson from fatal invasive fungal infections after CAR-T cell therapy: a case report and literature review

Review

作者: Ruixiang, Xia ; Jing, Ni ; Jifei, Dai ; Zhengfeng, Hou ; Danchen, Meng ; Zhonghui, Wu ; Zhangbiao, Long ; Jian, Ge ; Min, Ruan ; Xinglin, Liang

CD19 chimeric antigen receptor T (CAR-T) cell therapy represents an effective approach to treating patients with relapsed or refractory B-cell hematologic malignancies. Nevertheless, owing to the immunosuppressive effects of this regimen, patients undergoing CD19 CAR-T cell therapy may face an elevated risk of invasive fungal infections, which involve fungi penetrating the host's tissues or bloodstream, leading to life-threating infectious diseases. Herein, we present the case of a 17-year-old male diagnosed with acute lymphoblastic leukemia, who subsequently experienced a fatal invasive fungal infection following administration of CAR-T cell therapy. Furthermore, we delve into the identification of risk factors, implementation of preventive measures and exploration of therapeutic interventions for invasive fungal infections after CAR-T cell therapy.

100 项与 CD19 CAR - T Cell(Peking University People's Hospital) 相关的药物交易

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