Target intelligence / Profile preview

B-lymphocyte antigen CD20–MA-20–Natural killer group 2 member D Chimeric Antigen Receptor Synapse (CD20-MA20-NKG2D CAR)

Target
CD20-MA20-NKG2D CAR
Molecular classification
Chimeric Antigen Receptor, Immunological Synapse, Bispecific Adaptor Molecule, Receptor
01

Overview

The CD20–MA-20–NKG2D CAR synapse is a multi-component therapeutic complex designed to treat B-cell malignancies by redirecting T-cell cytotoxicity. It is the functional unit of the "convertibleCAR" platform, which consists of an inert T-cell expressing a modified Natural killer group 2 member D (NKG2D) receptor (ASP2802) and a bispecific adaptor molecule known as MA-20 (ASP101G or MicAbody) [1, 2]. The MA-20 adaptor contains an anti-CD20 binding domain and a mutated UL16-binding protein 2 (ULBP2) ligand that specifically engages the modified NKG2D CAR [1, 3]. When MA-20 binds simultaneously to CD20 on a tumor cell and the CAR on a T-cell, it creates a stable immunological synapse. This synapse initiates intracellular signaling through the CAR's CD3-zeta and 4-1BB domains, resulting in the release of perforins and granzymes to kill the target cell [1, 5]. This modular system is currently in clinical trials for relapsed or refractory B-cell lymphomas, providing a potential advantage in safety and flexibility over traditional CAR-T therapies [2, 5].

Other names
ASP2802-MA-20 complexCD20-targeting MicAbody-CAR synapseConvertible CAR-T synapseASP101G-ASP2802 interactionCD20-ULBP2-NKG2D complex
02

Mechanism of action

The MA-20 bispecific adaptor molecule bridges CD20-expressing tumor cells to NKG2D-based CAR-T cells (ASP2802), facilitating the formation of an immunological synapse that triggers T-cell activation and tumor cell lysis.

03

Biological functions

Immune responseCell-mediated cytotoxicitySignal transductionApoptosis
04

Disease associations

B-cell lymphomaNon-Hodgkin lymphomaB-cell malignanciesRelapsed or refractory B-cell lymphoma
05

Safety considerations

Cytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)B-cell aplasiaAnti-drug antibody (ADA) formation against the MA-20 adaptor
06

Interacting drugs

ASP2802

2 more in the full profile.

07

Biomarkers

B-lymphocyte antigen CD20 expressionNKG2D CAR expressionSerum cytokine levels (IL-6, IFN-gamma)Anti-drug antibodies (ADA) to MA-20

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