Anti-CD19 CAR-T as a feasible and safe treatment against central nervous system leukemia after intrathecal chemotherapy in adults with relapsed or refractory B-ALL

He, Xiaohua; Xiao, Xia; Li, Qing; Jiang, Yanyu; Cao, Yanjia; Sun, Rui; Jin, Xin; Tan, Yuan; Ji, Meng; Ma, Li; Lu, Wenyi; Lyu, Cuicui; Liu, Kaiqi; Zhao, Mingfeng

doi:10.1038/s41375-019-0437-5

Cited by 33 publications

(29 citation statements)

References 6 publications

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“…For extramedullary relapse (e.g., in the CNS and testes), CAR T cells can migrate and show anti-leukemia effects; therefore, they can be considered not only for isolated bone marrow relapses but also for isolated or combined extramedullary relapses, thereby avoiding radiation therapy [ 148 , 149 ].…”

Section: Emerging Therapy: Immunotherapymentioning

confidence: 99%

Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

Inaba

Pui

2021

JCM

114

105

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The outcomes of pediatric acute lymphoblastic leukemia (ALL) have improved remarkably during the last five decades. Such improvements were made possible by the incorporation of new diagnostic technologies, the effective administration of conventional chemotherapeutic agents, and the provision of better supportive care. With the 5-year survival rates now exceeding 90% in high-income countries, the goal for the next decade is to improve survival further toward 100% and to minimize treatment-related adverse effects. Based on genome-wide analyses, especially RNA-sequencing analyses, ALL can be classified into more than 20 B-lineage subtypes and more than 10 T-lineage subtypes with prognostic and therapeutic implications. Response to treatment is another critical prognostic factor, and detailed analysis of minimal residual disease can detect levels as low as one ALL cell among 1 million total cells. Such detailed analysis can facilitate the rational use of molecular targeted therapy and immunotherapy, which have emerged as new treatment strategies that can replace or reduce the use of conventional chemotherapy.

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Section: Emerging Therapy: Immunotherapymentioning

confidence: 99%

Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

Inaba

Pui

2021

JCM

114

105

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“…Treatment with T cells redirected to tumor specificity with a chimeric antigen receptor (CAR) may be well suited to treat intracranial tumors due to the ability of T cells to access the central nervous system (CNS) and migrate to infiltrative sites of disease. Treatment with CD19-directed CAR-T cells is effective not only against leptomeningeal leukemic infiltrates 5 but also brain parenchymal B-cell lymphomatous deposits 6 .…”

Section: Introductionmentioning

confidence: 99%

Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma

et al. 2021

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Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer, for which effective therapies are urgently needed. Chimeric antigen receptor (CAR)-based immunotherapy represents a promising therapeutic approach, but it is often impeded by highly immunosuppressive tumor microenvironments (TME). Here, in an immunocompetent, orthotopic GBM mouse model, we show that CAR-T cells targeting tumor-specific epidermal growth factor receptor variant III (EGFRvIII) alone fail to control fully established tumors but, when combined with a single, locally delivered dose of IL-12, achieve durable anti-tumor responses. IL-12 not only boosts cytotoxicity of CAR-T cells, but also reshapes the TME, driving increased infiltration of proinflammatory CD4+ T cells, decreased numbers of regulatory T cells (Treg), and activation of the myeloid compartment. Importantly, the immunotherapy-enabling benefits of IL-12 are achieved with minimal systemic effects. Our findings thus show that local delivery of IL-12 may be an effective adjuvant for CAR-T cell therapy for GBM.

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“…Given the fact that transduction with antigen-specific TCR can redirect T cell activity, the chimeric antigen receptor T cell (CAR-T) therapy has achieved a lot of success in treating cancers like leukemia, which may also provide a new way for the treatment of malignant solid tumors like prostate cancer [6][7][8][9]. Prostate-specific membrane antigen (PSMA) represents a suitable target for therapeutic purposes.…”

Section: Introductionmentioning

confidence: 99%

IL-23 and PSMA-targeted duo-CAR T cells in Prostate Cancer Eradication in a preclinical model

et al. 2020

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Background: Prostate cancer is one of the most common adult malignancies in men, and nearly all patients with metastatic prostate cancer can develop and receive resistance to primary androgen deprivation therapy (ADT), a state known as metastatic castration-resistant prostate cancer (mCRPC). Recent reports demonstrated the great breakthroughs made by the chimeric antigen receptor T (CAR-T) cell therapy, which is significantly different from traditional T cells therapies. In spite of the progress of CART technology in the treatment of lymphoma, leukemia, and other blood system tumor, there are still many difficulties in the treatment of solid tumors by CART technology. Methods: In this report, we designed a panel of IL23mAb-PSMA-CARs, including PSMA-CAR, IL23mAb-T2A-PSMA-CAR, IL23mAb-PSMA-CAR, and PSMA-CAR (soluble IL23mAb). And we studied the function of these CARs in mice model. Results: Co-culture experiments with different CAR T cells have normal lysis function in vitro. The duo-CAR T cells coexpressing the IL-23mAb and PSMA-mAb had a significant higher population than the rest three different CAR T cells in co-culturing experiments at day 28, 35 and 42. A panel of cytokines were differentially secreted at higher amounts in IL23mAb-T2A-PSMA-CAR T cells than CAR T cells in other groups. In NOD/SCID IL-2 gamma (NSG) mice model, IL23mAb-T2A-PSMA-CAR T cells functioned significantly better than CAR T cells from the other groups and eradicated the tumor from these mice starting at day 14 post T cells injection and regained the body weight immediately. In IL23mAb-T2A-PSMA-CAR mice, CD45RO+ CD8+ T cells and CD127+ CD4+ CAR T cells were significantly increased. RNA sequencing revealed a difference expression pattern of genes in IL23mAb-T2A-PSMA-CAR mice. A reverse infusion experiment under the same model further proved the tumor eradication function of IL23mAb-T2A-PSMA-CAR T cells. Conclusions: We found that IL-23mAb combined PSMA CARs worked better than PSMA CAR only in Prostate Cancer Eradication, and we further discussed the mechanisms among different IL-23mAb combined PSMA CARs in Prostate Cancer Eradication.

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Anti-CD19 CAR-T as a feasible and safe treatment against central nervous system leukemia after intrathecal chemotherapy in adults with relapsed or refractory B-ALL

Cited by 33 publications

References 6 publications

Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

Advances in the Diagnosis and Treatment of Pediatric Acute Lymphoblastic Leukemia

Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma

IL-23 and PSMA-targeted duo-CAR T cells in Prostate Cancer Eradication in a preclinical model

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