Delving into the Latest Updates on CT-032 with Synapse

Overview

Basic Info

Drug Type

Autologous CAR-T

Synonyms

CAR-CD19 T cells (CARsgen), CD19 Redirected Autologous Cells(CARsgen), CT032 CAR-CD19 T cells(CARsgen)

+ [1]

Target

CD19

Mechanism

CD19 modulators(B-lymphocyte antigen CD19 modulators), T lymphocyte replacements

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases

Active Indication

B-cell lymphoma recurrentB-cell lymphoma refractory

Inactive Indication-

Originator Organization

CARsgen Therapeutics Co. Ltd.

Active Organization

Carsgen Pharmaceuticals Co., Ltd.Startup

Inactive Organization

CARsgen Therapeutics Co. Ltd.

Drug Highest PhasePhase 1/2

First Approval Date-

Regulation-

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I期主要目的为评价CT032 CAR-CD19 T细胞注射液在复发/难治的非霍奇金B细胞淋巴瘤患者2个月的安全性和耐受性；确定CT032 CAR-CD19 T细胞的治疗的II期临床试验推荐剂量（RP2D）；II期主要目的为评价CT032 CAR-CD19 T细胞治疗R/R B-NHL患者6个月的疗效。

[Translation]

The main purpose of Phase I is to evaluate the safety and tolerability of CT032 CAR-CD19 T cell injection in patients with relapsed/refractory non-Hodgkin's B-cell lymphoma for 2 months; to determine the recommended dose (RP2D) of Phase II clinical trial for CT032 CAR-CD19 T cell treatment; the main purpose of Phase II is to evaluate the efficacy of CT032 CAR-CD19 T cell treatment in patients with R/R B-NHL for 6 months.

Start Date13 Aug 2019

Sponsor / Collaborator

Carsgen Pharmaceuticals Co., Ltd.Startup

100 Clinical Results associated with CT-032

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100 Translational Medicine associated with CT-032

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100 Patents (Medical) associated with CT-032

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88

Literatures (Medical) associated with CT-032

01 Jul 2024·Leukemia

Improved CAR-T cell activity associated with increased mitochondrial function primed by galactose

Article

Author: Gross, Golda ; Shbiro, Liat ; Zenab, Angi ; Itzhaki, Orit ; Aharoni-Tevet, Yarden ; Jacoby, Elad ; Alkadieri, Suha ; Meir, Amilia ; Yardeni, Tal ; Toren, Amos ; Ben Yosef, Shahar

CD19 CAR-T cells have led to durable remissions in patients with refractory B-cell malignancies; nevertheless, most patients eventually relapse in the long term. Many interventions aimed at improving current products have been reported, with a subset of them focusing on a direct or indirect link to the metabolic state of the CAR-T cells. We assessed clinical products from an ongoing clinical trial utilizing CD19-28z CAR-T cells from patients with acute lymphoblastic leukemia. CAR-T clinical products leading to a complete response had significantly higher mitochondrial function (by oxygen consumption rate) irrespective of mitochondrial content. Next, we replaced the carbon source of the media from glucose to galactose to impact cellular metabolism. Galactose-containing media increased mitochondrial activity in CAR-T cells, and improved in in-vitro efficacy, without any consistent phenotypic change in memory profile. Finally, CAR-T cells produced in galactose-based glucose-free media resulted in increased mitochondrial activity. Using an in-vivo model of Nalm6 injected mice, galactose-primed CAR-T cells significantly improved leukemia-free survival compared to standard glucose-cultured CAR-T cells. Our results prove the significance of mitochondrial metabolism on CAR-T cell efficacy and suggest a translational pathway to improve clinical products.

01 Apr 2024·Cancer Research

Immunometabolic Adaptation of CD19-Targeted CAR T Cells in the Central Nervous System Microenvironment of Patients Promotes Memory Development

Article

Author: Pirrotte, Patrick ; Singhal, Jyotsana ; Pathak, Khyatiben V. ; Aldoss, Ibrahim ; Wang, Xiuli ; Forman, Stephen J. ; Vyas, Vibhuti ; Haas, Eric R. ; Goldberg, Lior ; Garcia-Mansfield, Krystine ; Figarola, James L. ; Urak, Ryan

AbstractMetabolic reprogramming is a hallmark of T-cell activation, and metabolic fitness is fundamental for T-cell–mediated antitumor immunity. Insights into the metabolic plasticity of chimeric antigen receptor (CAR) T cells in patients could help identify approaches to improve their efficacy in treating cancer. Here, we investigated the spatiotemporal immunometabolic adaptation of CD19-targeted CAR T cells using clinical samples from CAR T-cell–treated patients. Context-dependent immunometabolic adaptation of CAR T cells demonstrated the link between their metabolism, activation, differentiation, function, and local microenvironment. Specifically, compared with the peripheral blood, low lipid availability, high IL15, and low TGFβ in the central nervous system microenvironment promoted immunometabolic adaptation of CAR T cells, including upregulation of a lipolytic signature and memory properties. Pharmacologic inhibition of lipolysis in cerebrospinal fluid led to decreased CAR T-cell survival. Furthermore, manufacturing CAR T cells in cerebrospinal fluid enhanced their metabolic fitness and antileukemic activity. Overall, this study elucidates spatiotemporal immunometabolic rewiring of CAR T cells in patients and demonstrates that these adaptations can be exploited to maximize the therapeutic efficacy of CAR T cells.Significance:The spatiotemporal immunometabolic landscape of CD19-targeted CAR T cells from patients reveals metabolic adaptations in specific microenvironments that can be exploited to maximize the therapeutic efficacy of CAR T cells.

01 Feb 2024·Bone Marrow Transplantation

Efficacy of CD19 directed therapies in patients with relapsed or refractory large b-cell lymphoma relapsing after CD19 directed chimeric antigen receptor T-cell therapy

Article

Author: Maakaron, Joseph E ; Fijalka, Andrew ; Craver, Emily ; Khurana, Arushi ; Li, Zhuo ; Epperla, Narendranath ; Bhaskar, Shakthi T ; Annunzio, Kaitlin ; Jagadeesh, Deepa ; Chavez, Julio ; Iqbal, Madiha ; Isufi, Iris ; Dholaria, Bhagirathbhai R ; Lin, Yi ; Kharfan-Dabaja, Mohamed A ; Rosenthal, Allison ; Mishra, Rahul ; Sandoval-Sus, Jose D ; Awan, Farrukh T ; Sumransub, Nuttavut ; Saha, Aditi ; Ivanov, Stanislav A

Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood. We conducted a multi-center study of patients with R/R LBCL that received either tafa-len or loncaT at any timepoint for R/R disease after CD19-CART therapy. Fifty-three patients were included in this study with the median follow up of 56 (9.1-199) weeks from CAR-T infusion. Median number of systemic therapies pre-CAR-T therapy was 3 (range: 1-6); axicabtagene ciloleucel was the most utilized CAR-T product (n = 32,60%). Median time from CAR-T therapy to tafa-len or loncaT was 7.3 (1.2-38.2) months with median number of lines of therapy between CAR-T therapy and these regimens of 1 (0-5). Combined overall response rate and complete response rates were 27% and 10%, respectively. Median duration of response was 13.3 (2.1-56.7) weeks. In this real-world study, the use of currently approved CD19-directed therapies to treat R/R LBCL after CD19-CAR-T therapy showed limited clinical activity and duration of responses.

100 Deals associated with CT-032

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
B-cell lymphoma recurrent	Phase 2	CN	Carsgen Pharmaceuticals Co., Ltd.Startup	13 Aug 2019
B-cell lymphoma refractory	Phase 2	CN	Carsgen Pharmaceuticals Co., Ltd.Startup	13 Aug 2019
B-Cell Lymphoma	Discovery	CN	CARsgen Therapeutics Co. Ltd.	23 Apr 2018