This is a single-arm, open-label, one center clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibodies (CTLA-4 and PD-1) and chimeric antigen receptor targeting epidermal growth factor receptor (EGFR-CAR) in adult patients with EGFR positive, advanced recurrent or refractory malignant solid tumors.

Start Date07 Jun 2017

Sponsor / Collaborator

Shanghai Cell Therapy Research Institute

100 Clinical Results associated with EGFR-CAR-T Cells(Shanghai Cell Therapy Research Institute)

100 Translational Medicine associated with EGFR-CAR-T Cells(Shanghai Cell Therapy Research Institute)

100 Patents (Medical) associated with EGFR-CAR-T Cells(Shanghai Cell Therapy Research Institute)

Literatures (Medical) associated with EGFR-CAR-T Cells(Shanghai Cell Therapy Research Institute)

01 Jun 2024·British journal of cancer

Single-cell sequencing reveals VEGFR as a potential target for CAR-T cell therapy in chordoma

Article

Author: Zhang, Boyan ; Zhang, Can ; Liu, Penghao ; Qi, Maoyang ; Wu, Huantong ; Chen, Zan ; Du, Yueqi ; Li, Xinqiang ; Duan, Wanru

BACKGROUND:

Chordomas are rare osseous neoplasms with a dismal prognosis when they recur. Here we identified cell surface proteins that could potentially serve as novel immunotherapeutic targets in patients with chordoma.

METHODS:

Fourteen chordoma samples from patients attending Xuanwu Hospital Capital Medical University were subjected to single-cell RNA sequencing. Target molecules were identified on chordoma cells and cancer metastasis-related signalling pathways characterised. VEGFR-targeting CAR-T cells and VEGFR CAR-T cells with an additional TGF-β scFv were synthesised and their in vitro antitumor activities were evaluated, including in a primary chordoma organoid model.

RESULTS:

Single-cell transcriptome sequencing identified the chordoma-specific antigen VEGFR and TGF-β as therapeutic targets. VRGFR CAR-T cells and VEGFR/TGF-β scFv CAR-T cells recognised antigen-positive cells and exhibited significant antitumor effects through CAR-T cell activation and cytokine secretion. Furthermore, VEGFR/TGF-β scFv CAR-T cells showed enhanced and sustained cytotoxicity of chordoma cell lines in vitro compared with VRGFR CAR-T cells.

CONCLUSIONS:

This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-β in chordoma progression. Our findings substantiate the potential of VEGFR as a target for CAR-T cell therapies in chordoma which, together with modulated TGF-β signalling, may augment the efficacy of CAR-T cells.

01 Nov 2023·International immunopharmacology

Dominant negative TGFβ receptor II and truncated TIM3 enhance the antitumor efficacy of CAR-T-cell therapy in prostate cancer

Article

Author: Huang, Houbao ; He, Lianjun ; Qian, Xueyi ; Shao, Huimin ; Xu, Zhenyu ; Tang, Lei ; Wang, Jiawei ; Wu, Yao

BACKGROUND:

The immune checkpoint molecules, Transforming growth factor beta receptor II (TGFβRII) and T cell immunoglobulin and mucin domain 3 (TIM3), have been identified as contributors to T cell immune suppression in prostate cancer. The objective of this investigation was to improve the tumor killing capability of prostate-specific membrane antigen (PSMA)-chimeric antigen receptor T (CAR-T) cells by targeting TIM3 and TGFβRII simultaneously.

METHODS:

To generate dnTGFβRII-trTIM3-PSMA-CAR-T (DT-PSMA-CAR-T) cells, the surface of PSMA-CAR-T cells was overexpressed with dominant negative TGFβRII (dnTGFβRII) and truncated extracellular TIM3 (trTIM3). The efficacy of DT-PSMA-CAR-T cells was assessed through in vitro killing experiments and animal experiments.

RESULTS:

The DT-PSMA-CAR-T cells demonstrated the ability to eradicate PSMA-positive prostate cancer cells, even in the presence of exogenous TGF-β and/or TIM3 activating antibodies. In addition, the cells demonstrated the ability to eliminate tumor tissue in an immunodeficient mouse model transplanted with GAL9-PSMA-PC3 cells in vitro, prolonging survival without significant toxic side effects.

CONCLUSIONS:

This study emphasizes that upregulating dnTGFβRII and trTIM3 on the surface of T cells can potentially diminish the inhibitory effects of TGFβRII and TIM3.

01 Nov 2023·Journal for immunotherapy of cancer

Framework humanization optimizes potency of anti-CD72 nanobody CAR-T cells for B-cell malignancies

Article

Author: Izgutdina, Adila ; Stieglitz, Elliot ; Nix, Matthew A ; Wiita, Arun P ; Naik, Akul ; Huang, Benjamin J ; Salangsang, Fernando ; Serrano, Juan Antonio Camara ; Phojanakong, Paul ; Ramos, Emilio ; Temple, William C ; Logan, Aaron C ; Young, Elizabeth P ; Steri, Veronica ; Wicaksono, Gianina ; Hermiston, Michelle ; Xirenayi, Simayijiang

Background:

Approximately 50% of patients who receive anti-CD19 CAR-T cells relapse, and new immunotherapeutic targets are urgently needed. We recently described CD72 as a promising target in B-cell malignancies and developed nanobody-based CAR-T cells (nanoCARs) against it. This cellular therapy design is understudied compared with scFv-based CAR-T cells, but has recently become of significant interest given the first regulatory approval of a nanoCAR in multiple myeloma.

Methods:

We humanized our previous nanobody framework regions, derived from llama, to generate a series of humanized anti-CD72 nanobodies. These nanobody binders were inserted into second-generation CD72 CAR-T cells and were evaluated against preclinical models of B cell acute lymphoblastic leukemia and B cell non-Hodgkin’s lymphoma in vitro and in vivo. Humanized CD72 nanoCARs were compared with parental (“NbD4”) CD72 nanoCARs and the clinically approved CD19-directed CAR-T construct tisangenlecleucel. RNA-sequencing, flow cytometry, and cytokine secretion profiling were used to determine differences between the different CAR constructs. We then used affinity maturation on the parental NbD4 construct to generate high affinity binders against CD72 to test if higher affinity to CD72 improved antitumor potency.

Results:

Toward clinical translation, here we humanize our previous nanobody framework regions, derived from llama, and surprisingly discover a clone (“H24”) with enhanced potency against B-cell tumors, including patient-derived samples after CD19 CAR-T relapse. Potentially underpinning improved potency, H24 has moderately higher binding affinity to CD72 compared with a fully llama framework. However, further affinity maturation (KD<1 nM) did not lead to improvement in cytotoxicity. After treatment with H24 nanoCARs, in vivo relapse was accompanied by CD72 antigen downregulation which was partially reversible. The H24 nanobody clone was found to have no off-target binding and is therefore designated as a true clinical candidate.

Conclusion:

This work supports translation of H24 CD72 nanoCARs for refractory B-cell malignancies, reveals potential mechanisms of resistance, and unexpectedly demonstrates that nanoCAR potency can be improved by framework alterations alone. These findings may have implications for future engineering of nanobody-based cellular therapies.

News (Medical) associated with EGFR-CAR-T Cells(Shanghai Cell Therapy Research Institute)

08 Apr 2024

·www.prnewswire.com

Verismo Therapeutics Announces Upcoming Presentation at AACR 2024

PHILADELPHIA, April 8, 2024 /PRNewswire/ -- Verismo Therapeutics, a clinical-stage CAR T company developing the novel KIR-CAR platform technology, today announced that an abstract has been accepted for poster presentation at the upcoming American Association for Cancer Research Annual Meeting 2024 (AACR 2024), to be held in San Diego on April 5-10, 2024. Presentation Details Title: Evaluating the relationship of affinity, functional avidity, and in vivo potency in KIR-CAR T cells Abstract Number: 6332 Date and Time: Tuesday, April 9th: 1:30 – 5:00 p.m. Presenting Author: Jun Xu, PhD Description: We have previously shown that a novel killer immunoglobulin receptor (KIR)-based CAR expressed in T cells as a multichain receptor with DAP12 (KIR-CAR T) has enhanced anti-tumor activity compared to conventional second-generation CAR T cells in several preclinical solid tumor models suggesting that this platform may show better activity in aggressive lymphoma. In this study, we aimed to evaluate the relationship of affinity, functional avidity, and in vivo potency of novel CD19 binders in a KIR-based CAR T cell. This study paves the way for developing an improved CD19-specific KIR-CAR T cell therapy for treating pts with B-cell malignancies. About the KIR-CAR Platform The KIR-CAR platform is a multi-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging tumor microenvironments. Using NK cell derived KIR and DAP12 split signaling provides a novel combined activation and co-stimulation separate from the usual T cell stimulation pathways. It also enables sustained chimeric receptor expression and improves KIR-CAR T cell long term function. This results in prolonged T cell functional persistence and leads to regression of solid tumors in preclinical models that are resistant to traditional CAR T cell therapies. The KIR-CAR platform is being investigated in combination with many additional emerging technologies to potentially provide the next-generation multimodal targeted immunotherapy for patients in need. About Verismo Therapeutics Verismo Therapeutics is a pioneer in multi-chain KIR-CAR technology, with its first asset SynKIR™-110 currently in a first-in-human Phase 1 clinical trial [NCT05568680] and its second asset, SynKIR™-310 targeting CD19-expressing r/r NHL, is currently under IND review by the FDA. Verismo is the only company developing the KIR-CAR platform, using a modified NK cell derived receptor and DAP12 pairing, designed to improve persistence and efficacy against aggressive tumors. The KIR-CAR platform technology was developed specifically for treating advanced solid tumors and B cell associated disorders and malignancies, areas of high unmet medical need. For more information, visit: CONTACT: Raymond Luke; [email protected] SOURCE Verismo Therapeutics

Phase 1ImmunotherapyAACRCell TherapyIND

100 Deals associated with EGFR-CAR-T Cells(Shanghai Cell Therapy Research Institute)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 2	CN	Shanghai Cell Therapy Research Institute	07 Jun 2017
EGFR mutation Solid Tumors	Phase 2	CN	Shanghai Cell Therapy Research Institute	07 Jun 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03182816 (pubmed \| J Cancer Res Clin Oncol) Manual	Phase 1	EGFR positive non-small cell lung cancer EGFR Positive	9	EGFR-specific CAR-T cells	nrgdycnuzt(glvcjrdbci) = fever vrwnnzopvu (mqiutrgdnn ) View more	Positive	01 Dec 2021

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

EGFR-CAR-T Cells(Shanghai Cell Therapy Research Institute)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation