Delving into the Latest Updates on T-Cells(Key Biologics) with Synapse

Overview

Basic Info

Drug Type

T-lymphocyte cell therapy

Synonyms-

Target-

Action-

Mechanism

Cell replacements

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Metastatic melanoma

Inactive Indication-

Originator Organization

Key Biologics LLC

Active Organization

Prometheus Biosciences, Inc.Key Biologics LLC

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Objectives:
The primary objective will be to determine whether patients receiving the combination of dendritic cells and high dose IL-2 (Cohort A) have sustained persistence of infused T cells compared to patients treated with T cells and high dose IL-2 alone.
Secondary endpoints will include evaluations for tumor response and studies to determine whether dendritic cells enhance the infused T cells in anti-tumor activity and their ability to migrate to the tumor site. In addition, we will evaluate the characteristics of the infused T cells that correspond with effectiveness in vivo.
Additionally, secondary objectives will include correlation of clinical parameters with survival (overall survival and progression-free survival) for all cohorts.
COHORT C
In a separate cohort (Cohort C) the primary endpoint will be the overall response rate of TIL treatment for patients who have not achieved PR or CR or have progressive disease from treatment of the BRAF inhibitor alone.
COHORT D
The primary objective of Cohort D is to confirm the safety of adoptively transferred, TIL into the CSF.
The secondary objective is the evaluation of clinical imaging and CSF response. Correlative objectives will assess if the intrathecally-infused T cells persist in the CSF, assess circulating tumor cells in the CSF, and assess various cytokine and other analyses,as feasible.
COHORT E
The primary objective of Cohort E is to determine the overall response rate of TIL treatment with cells grown by the TIL 3.0 pre-REP (Turnstile 1) phase of cellular growth.

Start Date01 Feb 2006

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

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100 Clinical Results associated with T-Cells(Key Biologics)

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100 Translational Medicine associated with T-Cells(Key Biologics)

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100 Patents (Medical) associated with T-Cells(Key Biologics)

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21

Literatures (Medical) associated with T-Cells(Key Biologics)

01 Feb 2024·Leukemia

Cellular dynamics following CAR T cell therapy are associated with response and toxicity in relapsed/refractory myeloma

Article

Author: Franke, Georg-Nikolaus ; Heyn, Simone ; Herling, Marco ; Merz, Maximilian ; Baber, Ronny ; Platzbecker, Uwe ; Weiss, Ronald ; Hell, Saskia ; Boldt, Andreas ; Kubasch, Anne Sophie ; Wang, Song Yau ; Ussmann, Jule ; Vucinic, Vladan ; Weidner, Heike ; Fischer, Luise ; Born, Patrick ; Franz, Paul ; Schwind, Sebastian ; Köhl, Ulrike ; Hoffmann, Sandra ; Jentzsch, Madlen ; Bach, Enrica ; Metzeler, Klaus H ; Kirchberg, Janine ; Reiche, Kristin ; Grieb, Nora ; Fricke, Stephan ; Seiffert, Sabine ; Sack, Ulrich

AbstractB-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM). However, data on cellular (CAR) T cell dynamics and the association with response, resistance or the occurrence of cytokine release syndrome (CRS) are limited. Therefore, we performed a comprehensive flow cytometry analysis of 27 RRMM patients treated with Idecabtagene vicleucel (Ide-cel) to assess the expansion capacity, persistence and effects on bystander cells of BCMA-targeting CAR T cells. Additionally, we addressed side effects, like cytokine release syndrome (CRS) and cytopenia. Our results show that in vivo expansion of CD8+ CAR T cells is correlated to response, however persistence is not essential for durable remission in RRMM patients. In addition, our data provide evidence, that an increased fraction of CD8+ T cells at day of leukapheresis in combination with successful lymphodepletion positively influence the outcome. We show that patients at risk for higher-grade CRS can be identified already prior to lymphodepletion. Our extensive characterization contributes to a better understanding of the dynamics and effects of BCMA-targeting CAR T cells, in order to predict the response of individual patients as well as side effects, which can be counteracted at an early stage or even prevented.

01 Jan 2024·European Journal of Haematology

Enhanced efficacy of CD19/CD22 bispecific CAR‐T cells with EAAAK linker on B‐cell malignancies

Article

Author: Zhang, Tingting ; Tian, Xiaopeng ; You, Fengtao ; Ma, Renyuxue ; Yang, Lin ; Tian, Shuaiyu ; Yang, Nan ; Wu, Hai ; An, Gangli ; Xiang, Shufen

AbstractObjectivesDespite the great success of CD19 CAR‐T cell therapy, its clinical efficacy has been greatly hampered by the high relapse rate. In this study, we designed and compared four structures of CD19/CD22 bispecific CAR‐T cells with different linkers and different orders of the antibody sequences.MethodsWe detected the cytotoxicity, cytokine secretion levels, sustainable killing ability, differentiation, exhaustion of these four CAR‐T cells in vitro. The optimal Bis‐C CAR‐T cells were evaluated the efficacy using NSG mice.ResultsThe two structures of CD19/CD22 bispecific CAR‐T cells using (EAAAK)3 as linker had more significant cytotoxicity and cytokine secretion levels. In the process of continuous killing, Bis‐C CAR‐T cells showed better sustained killing ability, memory phenotype differentiation, and exhaustion. In the in vivo experiment mimicking CD19‐negative relapse, Bis‐C CAR‐T was more able to control the tumor progression of mice in the CD19 low expression or no expression groups than CD19 CAR‐T.ConclusionsThis study has generated a novel bispecific CAR‐T cell that can simultaneously target CD19 or CD22 positive tumor cells, providing a new strategy to address the limitations of single‐targeted CAR‐T therapy in B‐cell tumors (limited response or relapse).

31 Dec 2023·OncoImmunology

Mesothelin-targeting T cells bearing a novel T cell receptor fusion construct (TRuC) exhibit potent antitumor efficacy against solid tumors

Article

Author: Geirut, Jessica ; Tighe, Robert ; Schrand, Brett ; Delgoffe, Greg ; Guyette, Sarah ; Hofmeister, Robert ; Menk, Ashley ; Ding, Jian ; Horton, Holly ; Guo, Guangwu ; Baeuerle, Patrick A.

T cell Receptor (TCR) Fusion Construct (TRuC®) T cells harness all signaling subunits of the TCR to activate T cells and eliminate tumor cells, with minimal release of cytokines. While adoptive cell therapy with chimeric antigen receptor (CAR)-T cells has shown unprecedented clinical efficacy against B-cell malignancies, monotherapy with CAR-T cells has suboptimal clinical efficacy against solid tumors, probably because of the artificial signaling properties of the CAR. TRuC-T cells may address the suboptimal efficacy of existing CAR-T therapies for solid tumors. Here, we report that mesothelin (MSLN)-specific TRuC-T cells (referred to as TC-210 T cells) potently kill MSLN+ tumor cells in vitro and efficiently eradicate MSLN+ mesothelioma, lung, and ovarian cancers in xenograft mouse tumor models. When benchmarked against MSLN-targeted BBζ CAR-T cells (MSLN-BBζ CAR-T cells), TC-210 T cells show an overall comparable level of efficacy; however, TC-210 T cells consistently show faster tumor rejection kinetics that are associated with earlier intratumoral accumulation and earlier signs of activation. Furthermore, in vitro and ex vivo metabolic profiling suggests TC-210 T cells have lower glycolytic activity and higher mitochondrial metabolism than MSLN-BBζ CAR-T cells. These data highlight TC-210 T cells as a promising cell therapy for treating MSLN-expressing cancers. The differentiated profile from CAR-T cells may translate into better efficacy and safety of TRuC-T cells for solid tumors.

100 Deals associated with T-Cells(Key Biologics)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic melanoma	Phase 2	United States	Prometheus Biosciences, Inc.	01 Feb 2006
Metastatic melanoma	Phase 2	United States	Key Biologics LLC	01 Feb 2006

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ICML2019	Not Applicable	Mantle-Cell Lymphoma	-	Lisocabtagene maraleucel dose level 1 (50 × 10 6 total CAR+ T cells)	(dzfyehivrq) = gjxjzdviid dllacsnnqx (dxtegudppi )	-	12 Jun 2019
ASGCT2011	Not Applicable	-	-	mIL15+CAR+ T cells	hzflneayfj(gbswhcfhbc) = cbjroegrvi ocisstccnj (egrgtxgipo )	-	01 May 2011
ASGCT2011	Not Applicable	-	-	IL-15 (CAR+ T cells)	hzflneayfj(gbswhcfhbc) = teaslwmtls ocisstccnj (egrgtxgipo )	-	01 May 2011
ASGCT2007	Not Applicable	-	-	VRX496-modified CD4+ T cells	daspykhpkx(ilifeocjbx) = biecroqykz addduaftdi (uzliuqwtxb ) View more	-	01 May 2007
VRX496 Phase II (ASGCT2006)	Phase 2	-	11	VRX496-modified HIV+, CD4+ T cells	mazwlzoblu(zfogkbwtor) = edlwgjttgr fepvdzlztt (zyjybkiehi ) View more	Positive	01 Aug 2006