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Last update 20 Mar 2025

CD70-CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

Last update 20 Mar 2025

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

CAR-NK

Synonyms

CD70 CAR-NK(The Second Affiliated Hospital Zhejiang University School of Medicine), CD70-targeted CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

Target

CD70

Action

modulators

Mechanism

CD70 modulators(CD70 antigen modulators)

Therapeutic Areas-

Active Indication-

Inactive Indication-

Originator Organization

Second Affiliated Hospital Zhejiang University College of

Active Organization

Second Affiliated Hospital Zhejiang University College of

Inactive Organization-

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Clinical Trials associated with CD70-CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

NCT06696846

/ Not yet recruitingPhase 1IIT

Cord Blood-derived CD70-targeting CAR-NK Cell Therapy for Refractory/relapsed T Cell Lymphoma and Acute Myeloid Leukemia

CD70 is a promising target for immunotherapy because it is overexpressed in T-cell lymphoma (TCL) and acute myeloid leukemia (AML) tumor cells but is found in deficient levels in normal tissues and hematopoietic stem cells. This study aims to evaluate the safety and efficacy of CD70-targeted CAR-NK (CD70-CAR-NK) cells in patients with relapsed and refractory TCL and AML.

Start Date01 Dec 2024

Sponsor / Collaborator

Second Affiliated Hospital Zhejiang University College of

100 Clinical Results associated with CD70-CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

100 Translational Medicine associated with CD70-CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

100 Patents (Medical) associated with CD70-CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

Literatures (Medical) associated with CD70-CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

01 Oct 2023·International journal of radiation oncology, biology, physics

Radiation Therapy Sensitizes Head-and-Neck Cancer Cells to Killing by Chimeric Antigen Receptor (CAR)-NK Cells Targeting CD70.

Article

Author: Li, Y ; Garza, L Melo ; Rezvani, K ; Dabaja, B ; Liu, B ; Uprety, N ; Islam, S ; Banerjee, P P ; Xu, A ; Daher, M ; Shrestha, R ; Kumar, B ; Manzar, G S ; Wang, X A ; Shanley, M ; Acharya, S ; Spiotto, M T ; Kaplan, M ; Rafei, H ; Basar, R

PURPOSE/OBJECTIVE(S)CAR-T cell therapy is limited by toxicity, high cost, logistical manufacturing issues in the autologous setting and risk of GVHD in the allogeneic setting. Substitution of T cells with NK cells opens the possibility for an allogeneic off-the-shelf product with a better safety profile. However, the inadequate efficacy of CAR-NK cells against solid tumors can be extrapolated from experience with CAR-T cells. There is limited but promising preclinical evidence that radiation therapy (RT) enhances CAR-T cell tumoricidal activity against solid tumors. However, there is no data examining the potential synergy between RT and CAR-NK cell therapy.MATERIALS/METHODSWe engineered CAR-NK cells with CD27 receptor as extracellular domain to target its natural ligand CD70, which is overexpressed in head-and-neck cancers (HNSCC). CAR-NK cell killing was assessed real-time through xCELLigence cytotoxicity assays. CD70+ OQ01 human HNSCCs were used for most experiments. FaDu is a CD70- HNSCC (negative ctrl). UMRC3 is a CD70+ kidney cancer cell line (positive ctrl). CD70 expression pre- and post-RT was assessed by flow cytometry and Western blot. Ionizing RT was compared at 5 doses: 0, 1.75, 3.5, 7, and 14 Gy. A single dose of 3.5 Gy was used for most experiments. Post-radiation effects were generally assessed at 3 days or 9 days post-RT. Intracellular staining was used to assess NK cell expression of IFN-γ, CD107a, and TNF-α by flow cytometry. CD27/CD70 interaction blockade was through α-CD27 pre-treatment of CAR-NK cells.RESULTSOQ01 HNSCCs heterogeneously express CD70 and are killed by CD70 CAR-NK cells in vitro. Pre-conditioning low-dose RT of 3.5 Gy applied to OQ01 HNSCCs 3 days prior to coculture with NK cells enhances CD70 CAR-NK cell killing, with ∼30% increased cytotoxicity against the tumor cells. Low-dose RT by itself did not induce acute cytolysis. As a possible mechanism for the increased sensitivity of irradiated OQ01 cells to CD70 CAR-NK cells, we found that RT enhances CD70 expression among HNSCCs in a dose-dependent manner. There was no increase in NK cell expression of IFN-γ, CD107a, and TNF-α with exposure to irradiated target cells. CD27/CD70 blockade does not solely abrogate RT-induced sensitization toward CAR-NK cell killing. Despite RT induction of transient increased expression of CD70, which normalizes by 9 days post-RT, there is persistent increase in RT-synergized target cell killing even at this later timepoint. Thus, altogether, RT sensitizes CD70-expressing HNSCC cells to CAR-NK cell killing in vitro.CONCLUSIONThis work represents the first preclinical study to identify the synergy of RT and CAR-NK cell therapy in solid tumors and is the first demonstration of CAR-NK cell activity against human HNSCCs. We show significantly enhanced potency of CAR-NK cells against irradiated tumor cells in vitro. Collectively, this research will be vital to guide efforts expanding into other target antigens and tumor types.

100 Deals associated with CD70-CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

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CD70-CAR-NK cells(The Second Affiliated Hospital Zhejiang University School of Medicine)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation