The primary objective of this study is to evaluate the safety and clinical activity of NKG2D-based CAR-T cells infusion in the treatment of relapsed/refractory NKG2DL+ solid tumors.

Start Date01 Mar 2021

Sponsor / Collaborator

Fudan University

[+1]

100 Clinical Results associated with NKG2D-based CAR T-cells(Nanjing KAEDI Biotech, Inc.)

100 Translational Medicine associated with NKG2D-based CAR T-cells(Nanjing KAEDI Biotech, Inc.)

100 Patents (Medical) associated with NKG2D-based CAR T-cells(Nanjing KAEDI Biotech, Inc.)

Literatures (Medical) associated with NKG2D-based CAR T-cells(Nanjing KAEDI Biotech, Inc.)

01 Oct 2023·Heliyon

Lenalidomide improves NKG2D-based CAR-T cell activity against colorectal cancer cells invitro

Article

Author: Abdoli, Shahriyar ; Shahbazi, Majid ; Farazmandfar, Touraj ; Zarei, Mahdi

IntroductionAlthough CAR-based immunotherapy is viewed as a promising treatment for tumors, particularly hematological malignancies, solid tumors can pose challenges. It has been suggested that the immunomodulatory medication Lenalidomide (LEN) may increase the effectiveness of CAR T cells in the treatment of solid tumors. The purpose of our study was to investigate the effect of NKG2D-based CAR T cell therapy on colorectal cancer cell lines, and then we assessed combinatorial therapy using NKG2D CAR T cells and lenalidomide in vitro.Methods and resultsTo prepare NKG2D CAR T cells, a second-generation NKG2D-CAR construct was designed and transfected into the T cells using a lentiviral system. The NKG2D CAR T cells showed significantly higher cytotoxic activity against colorectal cancer cell lines, HCT116 and SW480, compared to untransduced T cells. In addition, our data demonstrated that the cytotoxicity and cytokine secretion of NKG2D CAR T cells significantly increased in the presence of higher doses of lenalidomide.ConclusionsThe study findings suggest that combinational therapy, utilizing NKG2D-based CAR T cells and lenalidomide, has a high potential for effectively eliminating tumor cells in vitro.

01 Nov 2019·Cancer Immunology ResearchQ1 · MEDICINE

Eradication of Hepatocellular Carcinoma by NKG2D-Based CAR-T Cells

Q1 · MEDICINE

Article

Author: Zhao, Xudong ; Cai, Changchun ; Yang, Dong ; Sun, Bin ; Xu, Jianming ; Cui, Xiaoyue ; Jia, Ru ; Dai, Hongjiu ; Liu, Xiuyun ; Li, Wenxuan

AbstractDespite the great success of chimeric antigen receptor T (CAR-T)–cell therapy in the treatment of hematologic malignancies, CAR-T–cell therapy is limited in solid tumors, including hepatocellular carcinoma (HCC). NK group 2 member D (NKG2D) ligands (NKG2DL) are generally absent on the surface of normal cells but are overexpressed on malignant cells, offering good targets for CAR-T therapy. Indeed, analysis of The Cancer Genome Atlas and HCC tumor samples showed that the expression of most NKG2DLs was elevated in tumors compared with normal tissues. Thus, we designed a novel NKG2D-based CAR comprising the extracellular domain of human NKG2D, 4-1BB, and CD3ζ signaling domains (BBz). NKG2D-BBz CAR-T cells efficiently killed the HCC cell lines SMMC-7721 and MHCC97H in vitro, which express high levels of NKG2DLs, whereas they less efficiently killed NKG2DL-silenced SMMC-7721 cells or NKG2DL-negative Hep3B cells. Overexpression of MICA or ULBP2 in Hep3B improved the killing capacity of NKG2D-BBz CAR-T cells. T cells expressing the NKG2D-BBz CAR effectively eradicated SMMC-7721 HCC xenografts. Collectively, these results suggested that NKG2D-BBz CAR-T cells could potently eliminate NKG2DL-high HCC cells both in vitro and in vivo, thereby providing a promising therapeutic intervention for patients with NKG2DL-positive HCC.

15 Feb 2018·Cancer ResearchQ1 · MEDICINE

NKG2D-Based CAR T Cells and Radiotherapy Exert Synergistic Efficacy in Glioblastoma

Q1 · MEDICINE

Article

Author: Sentman, Charles L. ; Guckenberger, Matthias ; Weiss, Tobias ; Weller, Michael ; Roth, Patrick

AbstractChimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T-cell therapy into conventional anticancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models. ChNKG2D T cells demonstrated high IFNγ production and cytolytic activity in vitro. Upon systemic administration in vivo, chNKG2D T cells migrated to the tumor site in the brain, did not induce adverse events, prolonged survival, and cured a fraction of glioma-bearing mice. Surviving mice were protected long-term against tumor rechallenge. Mechanistically, this was not solely the result of a classical immune memory response, but rather involved local persistence of chNKG2D T cells. A subtherapeutic dose of local radiotherapy in combination with chNKG2D T-cell treatment resulted in synergistic activity in two independent syngeneic mouse glioma models by promoting migration of CAR T cells to the tumor site and increased effector functions. We thus provide preclinical proof-of-concept of NKG2D CAR T-cell activity in mouse glioma models and demonstrate efficacy, long-term persistence, and synergistic activity in combination with radiotherapy, providing a rationale to translate this immunotherapeutic strategy to human glioma patients.Significance: These findings provide evidence for synergy of conventional anticancer therapy and CAR T cells and heralds future studies for other treatment combinations. Cancer Res; 78(4); 1031–43. ©2017 AACR.

100 Deals associated with NKG2D-based CAR T-cells(Nanjing KAEDI Biotech, Inc.)

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
NKG2DL Positive Solid Tumors	Phase 2	CN	Nanjing KAEDI Biotech, Inc.	01 Mar 2021
Colonic Cancer	Phase 1	CN	Nanjing KAEDI Biotech, Inc.	01 Mar 2021
Glioblastoma	Phase 1	CN	Nanjing KAEDI Biotech, Inc.	01 Mar 2021
Hepatocellular Carcinoma	Phase 1	CN	Nanjing KAEDI Biotech, Inc.	01 Mar 2021
Medulloblastoma	Phase 1	CN	Nanjing KAEDI Biotech, Inc.	01 Mar 2021

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