Target Information

Target General Information

Target ID

T12097 (Former ID: TTDR00773)

Target Name

Melanoma-associated antigen 4 (MAGEA4)

Synonyms

MAGE4; MAGE-X2 antigen; MAGE-X2; MAGE-41 antigen; MAGE-41; MAGE-4 protein; MAGE-4 antigen; Cancer/testis antigen 1.4; CT1.4

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Gene Name

MAGEA4

Target Type

Clinical trial target

[1]

Disease

[+] 4 Target-related Diseases

Kaposi sarcoma [ICD-11: 2B57]

Synovial sarcoma [ICD-11: 2B5A]

Lung cancer [ICD-11: 2C25]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Function

Not known, though may play a role in embryonal development and tumor transformation or aspects of tumor progression.

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BioChemical Class

Melanoma associated antigen

UniProt ID

MAGA4_HUMAN

Sequence

MSSEQKSQHCKPEEGVEAQEEALGLVGAQAPTTEEQEAAVSSSSPLVPGTLEEVPAAESA
GPPQSPQGASALPTTISFTCWRQPNEGSSSQEEEGPSTSPDAESLFREALSNKVDELAHF
LLRKYRAKELVTKAEMLERVIKNYKRCFPVIFGKASESLKMIFGIDVKEVDPASNTYTLV
TCLGLSYDGLLGNNQIFPKTGLLIIVLGTIAMEGDSASEEEIWEELGVMGVYDGREHTVY
GEPRKLLTQDWVQENYLEYRQVPGSNPARYEFLWGPRALAETSYVKVLEHVVRVNARVRI
AYPSLREAALLEEEEGV

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

ADP-A2M4

Drug Info

Phase 2

Synovial sarcoma

[2]

Afamitresgene autoleucel

Drug Info

Phase 2

Soft tissue sarcoma

[3]

CAR-T cells targeting MAGE-A4

Drug Info

Phase 1/2

Lung cancer

[1]

Mode of Action

[+] 1 Modes of Action

CAR-T-Cell-Therapy

[+] 1 CAR-T-Cell-Therapy drugs

CAR-T cells targeting MAGE-A4

Drug Info

[1]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

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Ligand Name: 2-(2-{2-[2-(2-Methoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-ethanol

Ligand Info

Structure Description

CRYSTAL STRUCTURE OF HLA-A*0201/MAGE-A4-PEPTIDE COMPLEX

PDB:1I4F

Method

X-ray diffraction

Resolution

1.40 Å

Mutation

[5]

PDB Sequence

GVYDGREHTV

¹⁰

Residue

Distance (Å)

ASP4

4.731

Residue

Distance (Å)

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Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Similarity Proteins Human Tissue Distribution

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Similarity Proteins

Human Tissue Distribution

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Melanoma-associated antigen C2 (MAGEC2)		50.000 (109/218)	2.24E-60
Melanoma-associated antigen C3 (MAGEC3)		50.382 (66/131)	6.40E-33


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

Target Regulators

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Target-interacting Proteins

Target-interacting Proteins Info

References

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REF 1

ClinicalTrials.gov (NCT03356808) Antigen-specific T Cells Against Lung Cancer

REF 2

Clinical pipeline report, company report or official report of Adaptimmune.

REF 3

ClinicalTrials.gov (NCT04044768) A Phase 2 Single Arm Open-Label Clinical Trial of ADP-A2M4 SPEAR? T Cells in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma. U.S.National Institutes of Health.

REF 4

Autologous T cell therapy for MAGE-A4(+) solid cancers in HLA-A*02(+) patients: a phase 1 trial. Nat Med. 2023 Jan;29(1):104-114.

REF 5

High-resolution structure of HLA-A*0201 in complex with a tumour-specific antigenic peptide encoded by the MAGE-A4 gene. J Mol Biol. 2001 Jul 27;310(5):1167-76.

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