Allogeneic NKG2DL-targeting CAR γδ T Cells (CTM-N2D) in Advanced Cancers (ANGELICA)

Summary

CAR-T is a pioneering cancer treatment which has found success in some cancers. This treatment is made first by taking blood cells from the patient. Then in the lab, an artificial protein - a Chimeric Antigen Receptor (CAR), is grafted on the surface of immune cells. The modified cells, which are readministered to the patient, have enhanced abilities to target and destroy cancers than unmodified immune cells.

Currently approved CAR-T can only be used autologously. i.e. the patient will receive CAR-T treatment made from their own cells. This is because current CAR-T treatment uses αβ T cells - a type of immune cell which are largely non-transferable between individual human beings due to the high risk of Graft-versus-Host Disease. However, autologous CAR-T comes with many limitations. A lengthy, manufacturing process follows after the patient donates their own blood, accompanied by a high risk of manufacturing failure, which can be attributed to the cell quality from cancer patients undergoing stressful anti-cancer therapy.

CytoMed Therapeutics pioneers a new CAR-T treatment (CTM-N2D) which may confer some benefit over current CAR-T treatment. CTM-N2D uses a subtype of immune cell -- γδ T cell. Secondly, the CAR on CTM-N2D targets a surface antigen called NKG2DL which are commonly present in many cancer. These two features may confer a safer product profile, of better quality and may be efficacious in cancers where previous CAR-T treatments has not.

The phase I clinical trial of CTM-N2D will be conducted at the National University Hospital, Singapore. The objective of this clinical trial is to determine the optimal dose of CTM-N2D, and to investigate its safety and tolerability. The subjects of the clinical trial will also be investigated for their tumour response to CTM-N2D.

CTM-N2D has undergone preclinical studies. Relevant data from other clinical trials are also used to infer the expected outcome, and strategies of management of this clinical trial. The institution's ethical review board must give its approval before the study may begin. An independent Data Safety Monitoring Board monitors the safety aspect of this trial.

Conditions

• Cancer
• Malignancy
• Refractory Cancer
• Relapsed Cancer

Interventions

BIOLOGICAL

Allogeneic NKG2DL-targeting Chimeric Antigen Receptor-grafted γδ T Cells (CTM-N2D)

In the production of CTM-N2D, blood cells from healthy donors are used as starting materials. Through a proprietary expansion technology, γδ T cells of high-purity can be obtained. These γδ T cells are further grafted with NKG2DL-targeting CARs using mRNA electroporation to enhance its anticancer potency. The finished product (CTM-N2D) are then infused allogeneically into cancer patients.

Sponsors & Collaborators

• National University Hospital, Singapore

  collaborator OTHER

• CytoMed Therapeutics Pte Ltd

  lead INDUSTRY

Principal Investigators

• Anand D Jeyasekharan, Dr · National University Health System (NUHS)

• Jieming Zeng, Dr · CytoMed Therapeutics Pte Ltd

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-11-19

Primary Completion

2025-11-30

Completion

2026-12-31

Countries

• Singapore

Study Locations