EGFR antagonists(Epidermal growth factor receptor erbB1 antagonists), HPK1 inhibitors(Mitogen-activated protein kinase kinase kinase kinase 1 inhibitors), PD-1 inhibitors(Programmed cell death protein 1 inhibitors)

+ [2]

Therapeutic Areas

NeoplasmsNervous System DiseasesDigestive System Disorders+ [2]

Active Indication

Advanced Malignant Solid NeoplasmBrain CancerBreast Cancer+ [3]

Inactive Indication-

Originator Organization

Guangdong Zhaotai InVivo Biomedicine Co. Ltd.

Active Organization

Guangdong Zhaotai InVivo Biomedicine Co. Ltd.

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Clinical Trials associated with EGFR-TILs(Guangdong Zhaotai InVivo Biomedicine)

NCT04842812 / RecruitingPhase 1IIT

Engineered TILs/CAR-TILs With PD1 Knockout and Anti-PD1/CTLA4-scFv Secreting or CARs Against Various Antigens to Treat Advanced Solid Tumors

Tumor infiltration lymphocytes (TILs) have been harvested from advanced cancer patients and constructed to knockout PD1 gene and express scFvs against both PD1 and CTALA4 and CARs against various antigens, followed by transfusion into the patients. The safety, tolerance, and preliminary clinical efficacy of the TILs will be evaluated.

Start Date01 Jan 2021

Sponsor / Collaborator

Second Affiliated Hospital of Guangzhou Medical University

[+1]

100 Clinical Results associated with EGFR-TILs(Guangdong Zhaotai InVivo Biomedicine)

100 Translational Medicine associated with EGFR-TILs(Guangdong Zhaotai InVivo Biomedicine)

100 Patents (Medical) associated with EGFR-TILs(Guangdong Zhaotai InVivo Biomedicine)

Literatures (Medical) associated with EGFR-TILs(Guangdong Zhaotai InVivo Biomedicine)

01 Sep 2023·Journal of Cancer Research and Clinical Oncology

CD4−/CD8− double-negative tumor-infiltrating lymphocytes expanded from solid tumor tissue suppress the proliferation of tumor cells in an MHC-independent way

Article

Author: Xie, Rongjia ; Li, Yue ; Xu, Qing ; Zhang, Qian ; Lu, Jingyi ; He, Rong ; Huang, Chen ; Guo, Xianling

PURPOSETumor-infiltrating lymphocytes (TILs) have shown remarkable clinical responses in some patients with advanced solid tumors. As a rare subset of TILs, CD4^-/CD8^- double-negative T cells (DNTs) were poorly known. This study aims to investigate the characteristics and function of CD3⁺CD4^-CD8^- TILs (double-negative TIL, DN-TILs) derived from solid tumor.METHODSDN-TILs were derived and expanded ex vivo from resected gastric carcinoma tissue and phenotyped by flow cytometry. The cytotoxicity of DN-TILs was determined against established tumor cell lines in vitro or through in vivo adoptive transfer into xenograft models. K562 cells were transferred with the HLA gene to verify whether the cytotoxicity of DN-TILs was MHC-independent.RESULTSFlow cytometric analysis revealed a high-purity population of DN-TILs (> 97%) within CD3⁺ TILs, which expanded more than 800-folds in 2 weeks, consisting of a mixture of alpha-beta (αβ) and gamma-delta (γδ) T-cell receptor (TCR)-expressing cells (with the majority being αβ-TCR, > 95%). Using single-cell RNA sequencing, the expanded DN-TILs were categorized into four main subsets, Natural Killer T cells (approximately 80%, 5563 in 7028), Progenitor cells, Germ cells and T helper2 cells. DN-TILs exhibited a broad anticancer cytotoxicity in a donor-unrestricted manner against various cancer cell lines derived from pancreatic cancer (Panc-1), gastric cancer (HGC-27), ovarian cancer (SKOV-3), malignant melanoma (A375). The cytotoxicity was MHC-independent, which was not altered in K562 transferring with HLA gene or not. DN-TILs significantly reduced tumor volume in xenograft models with superior tumor-homing ability and low off-target toxicity.CONCLUSIONGastric carcinoma derived DN-TIL can target tumor cells in vitro and in vivo. DN-TILs have the potential to be used as a adoptive cell therapy for solid cancers with both the advantages of DNT and TIL.

100 Deals associated with EGFR-TILs(Guangdong Zhaotai InVivo Biomedicine)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	CN	Guangdong Zhaotai InVivo Biomedicine Co. Ltd.	01 Jan 2021
Brain Cancer	Phase 1	CN	Guangdong Zhaotai InVivo Biomedicine Co. Ltd.	01 Jan 2021
Breast Cancer	Phase 1	CN	Guangdong Zhaotai InVivo Biomedicine Co. Ltd.	01 Jan 2021
Colorectal Cancer	Phase 1	CN	Guangdong Zhaotai InVivo Biomedicine Co. Ltd.	01 Jan 2021
Liver Cancer	Phase 1	CN	Guangdong Zhaotai InVivo Biomedicine Co. Ltd.	01 Jan 2021
Lung Cancer	Phase 1	CN	Guangdong Zhaotai InVivo Biomedicine Co. Ltd.	01 Jan 2021

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