Exploratory Study on the Treatment of Advanced Solid Tumor With Non-viral Vector Multi-targeted Autosecretory Multifunctional Antibody CAR-T Cell Injection

The main goal of this trial is to evaluate the safety and tolerability of CAR T cell therapy for advanced solid tumors with positive mesothelin and MUC1.Patients were screened, peripheral blood mononuclear cells (PBMC) were isolated from eligible patients, and cells were prepared. Pretreatment was performed within 5 days before infusion, and CAR T cells were infused on day 0 (the dose was determined according to the requirements of climbing/expansion). The safety intensive observation period was 28 days after infusion, and the clinical efficacy after infusion was evaluated on days 28-34. The follow-up observation and evaluation were carried out according to the follow-up visit point, and the follow-up period was 1 year. From the second year, the telephone follow-up period was entered.

开始日期2024-03-07

申办/合作机构

上海细胞治疗集团有限公司

NCT06249256 / Recruiting早期临床1期

An Exploratory Study on the Treatment of Advanced Solid Tumors by Secretory PD1 Nanoantibody Targeting Mesothelin Fast CAR T Cells

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of fast autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies in patients with solid tumors.

开始日期2023-06-01

申办/合作机构

上海细胞治疗集团有限公司

100 项与 Fast Autologous MSLN-CAR-T Cells Secreting PD-1 Nanobodies(Shanghai Cell Therapy Group) 相关的临床结果

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100 项与 Fast Autologous MSLN-CAR-T Cells Secreting PD-1 Nanobodies(Shanghai Cell Therapy Group) 相关的转化医学

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100 项与 Fast Autologous MSLN-CAR-T Cells Secreting PD-1 Nanobodies(Shanghai Cell Therapy Group) 相关的专利（医药）

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102

项与 Fast Autologous MSLN-CAR-T Cells Secreting PD-1 Nanobodies(Shanghai Cell Therapy Group) 相关的文献（医药）

2024-08-15·Clinical Cancer Research

Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers

Article

作者: Altvater, Bianca ; Rossig, Claudia ; von Döllen, Angelika ; Dreger, Celine ; Völkl, Simon ; Schambach, Axel ; Petry, Katja ; Zimmermann, Katharina ; Jungblut, Melanie ; Kailayangiri, Sareetha ; Mackensen, Andreas ; Görlich, Dennis ; Kretschmann, Sascha ; Fischer-Riepe, Lena ; Hartley, Jordan ; Lode, Holger ; Abken, Hinrich ; Hartmann, Wolfgang ; Pfeifer, Rita ; Bosio, Andreas ; Aigner, Michael

AbstractPurpose:Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR T cells) is a promising principle to overcome the limited activity of canonical CAR T cells against solid cancers.Experimental Design:We developed an investigational medicinal product, GD2IL18CART, consisting of CAR T cells directed against ganglioside GD2 with CAR-inducible IL18 to enhance their activation response and cytolytic effector functions in the tumor microenvironment. To allow stratification of patients according to tumor GD2 expression, we established and validated immunofluorescence detection of GD2 on paraffin-embedded tumor tissues.Results:Lentiviral all-in-one vector engineering of human T cells with the GD2-specific CAR with and without inducible IL18 resulted in cell products with comparable proportions of CAR-expressing central memory T cells. Production of IL18 strictly depends on GD2 antigen engagement. GD2IL18CART respond to interaction with GD2-positive tumor cells with higher IFNγ and TNFα cytokine release and more effective target cytolysis compared with CAR T cells without inducible IL18. GD2IL18CART further have superior in vivo antitumor activity, with eradication of GD2-positive tumor xenografts. Finally, we established GMP-compliant manufacturing of GD2IL18CART and found it to be feasible and efficient at clinical scale.Conclusions:These results pave the way for clinical investigation of GD2IL18CART in pediatric and adult patients with neuroblastoma and other GD2-positive cancers (EU CT 2022– 501725–21–00).See related commentary by Locatelli and Quintarelli, p. 3361

2024-07-01·Cancer Discovery

CD70-Targeted Allogeneic CAR T-Cell Therapy for Advanced Clear Cell Renal Cell Carcinoma

Article

作者: Tran, Ben ; Agarwal, Neeraj ; Harrison, Simon J. ; Keegan, Alissa ; Haanen, John B.A.G. ; Tannir, Nizar M. ; Morrow, Phuong K. ; Pal, Sumanta K. ; Karnik, Sushant ; Patel, Sagar S. ; Heath, Heidi ; Meza, Luis ; Dar, Henia ; Gurary, Ellen B. ; Hurwitz, Michael E. ; Dequeant, Mary-Lee ; Yuen, Rachel R. ; Srour, Samer A. ; Guo, Changan ; He, Qiuling Ally ; Ma, Anna ; Budde, Lihua E. ; Williams, Leah M. ; Klobuch, Sebastian ; Sacher, Adrian

AbstractTherapeutic approaches for clear cell renal cell carcinoma (ccRCC) remain limited; however, chimeric antigen receptor (CAR) T-cell therapies may offer novel treatment options. CTX130, an allogeneic CD70-targeting CAR T-cell product, was developed for the treatment of advanced or refractory ccRCC. We report that CTX130 showed favorable preclinical proliferation and cytotoxicity profiles and completely regressed RCC xenograft tumors. We also report results from 16 patients with relapsed/refractory ccRCC who received CTX130 in a phase I, multicenter, first-in-human clinical trial. No patients encountered dose-limiting toxicity, and disease control was achieved in 81.3% of patients. One patient remains in a durable complete response at 3 years. Finally, we report on a next-generation CAR T construct, CTX131, in which synergistic potency edits to CTX130 confer improved expansion and efficacy in preclinical studies. These data represent a proof of concept for the treatment of ccRCC and other CD70+ malignancies with CD70− targeted allogeneic CAR T cells.Significance: Although the role of CAR T cells is well established in hematologic malignancies, the clinical experience in solid tumors has been disappointing. This clinical trial demonstrates the first complete response in a patient with RCC, reinforcing the potential benefit of CAR T cells in the treatment of solid tumors.See corresponding author Sumanta K. Pal discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932606570/887520f9cb

2024-06-01·Transplantation and Cellular Therapy

INSPIRED Symposium Part 5: Expanding the Use of CAR T Cells in Children and Young Adults

Review

作者: Grupp, Stephan A ; Moskop, Amy ; Rouce, Rayne ; Aplenc, Richard ; Fabrizio, Vanessa A ; McNerney, Kevin O ; Talleur, Aimee C ; Mackall, Crystal ; Nguyen, Rosa ; Majzner, Robbie

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable efficacy in relapsed/refractory (r/r) B cell malignancies, including in pediatric patients with acute lymphoblastic leukemia (ALL). Expanding this success to other hematologic and solid malignancies is an area of active research and, although challenges remain, novel solutions have led to significant progress over the past decade. Ongoing clinical trials for CAR T cell therapy for T cell malignancies and acute myeloid leukemia (AML) have highlighted challenges, including antigen specificity with off-tumor toxicity and persistence concerns. In T cell malignancies, notable challenges include CAR T cell fratricide and prolonged T cell aplasia, which are being addressed with strategies such as gene editing and suicide switch technologies. In AML, antigen identification remains a significant barrier, due to shared antigens across healthy hematopoietic progenitor cells and myeloid blasts. Strategies to limit persistence and circumvent the immunosuppressive tumor microenvironment (TME) created by AML are also being explored. CAR T cell therapies for central nervous system and solid tumors have several challenges, including tumor antigen heterogeneity, immunosuppressive and hypoxic TME, and potential for off-target toxicity. Numerous CAR T cell products have been designed to overcome these challenges, including "armored" CARs and CAR/T cell receptor (TCR) hybrids. Strategies to enhance CAR T cell delivery, augment CAR T cell performance in the TME, and ensure the safety of these products have shown promising results. In this manuscript, we will review the available evidence for CAR T cell use in T cell malignancies, AML, central nervous system (CNS), and non-CNS solid tumor malignancies, and recommend areas for future research.

100 项与 Fast Autologous MSLN-CAR-T Cells Secreting PD-1 Nanobodies(Shanghai Cell Therapy Group) 相关的药物交易

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