Target Information

Target General Information

Target ID

T71205

Target Name

Myeloid inhibitory C-type lectin-like receptor (CD371)

Synonyms

MICL; Dendritic cell-associated lectin 2; DCAL2; DCAL-2; CLL1; CLL-1; C-type lectin-like molecule 1; C-type lectin domain family 12 member A

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Gene Name

CLEC12A

Target Type

Clinical trial target

[1]

Disease

[+] 1 Target-related Diseases

Acute myeloid leukaemia [ICD-11: 2A60]

Function

Cell surface receptor that modulates signaling cascades and mediates tyrosine phosphorylation of target MAP kinases.

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UniProt ID

CL12A_HUMAN

Sequence

MSEEVTYADLQFQNSSEMEKIPEIGKFGEKAPPAPSHVWRPAALFLTLLCLLLLIGLGVL
ASMFHVTLKIEMKKMNKLQNISEELQRNISLQLMSNMNISNKIRNLSTTLQTIATKLCRE
LYSKEQEHKCKPCPRRWIWHKDSCYFLSDDVQTWQESKMACAAQNASLLKINNKNALEFI
KSQSRSYDYWLGLSPEEDSTRGMRVDNIINSSAWVIRNAPDLNNMYCGYINRLYVQYYHC
TYKKRMICEKMANPVQLGSTYFREA

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 8 Clinical Trial Drugs

CD123/CLL1 CAR-T Cells

Drug Info

Phase 2/3

Acute myeloid leukaemia

[1]

CLL1 CAR-T Cell

Drug Info

Phase 2/3

Acute myeloid leukaemia

[1]

CAR-T cells targeting CLL1

Drug Info

Phase 1/2

leukaemia

[2]

CLL1-specific gene-engineered T cells

Drug Info

Phase 1/2

Acute myeloid leukaemia

[3]

CLL1-CD33 cCART cell therapy

Drug Info

Phase 1

Acute myeloid leukaemia

[4]

CLT030

Drug Info

Phase 1

Acute myeloid leukaemia

[5]

KITE-222

Drug Info

Phase 1

Acute myeloid leukaemia

[6]

Tepoditamab

Drug Info

Phase 1

Acute myelogenous leukaemia

[7]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

UCART-CLL1

Drug Info

Preclinical

Multiple myeloma

[8]

Mode of Action

[+] 2 Modes of Action

CAR-T-Cell-Therapy(Dual specific)

[+] 2 CAR-T-Cell-Therapy(Dual specific) drugs

CD123/CLL1 CAR-T Cells

Drug Info

[1]

CLL1 CAR-T Cell

Drug Info

[1]

CAR-T-Cell-Therapy

[+] 2 CAR-T-Cell-Therapy drugs

CAR-T cells targeting CLL1

Drug Info

[2]

CLL1-specific gene-engineered T cells

Drug Info

[3]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

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
Putative C-type lectin-like domain family 1 (CLECL1P)		33.333 (16/48)	4.00E-03


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.

References

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REF 1

ClinicalTrials.gov (NCT03631576) CD123/CLL1 CAR-T Cells for R/R AML

REF 2

ClinicalTrials.gov (NCT03312205) CAR-T Cells for Relapsed or Refractory Haematopoietic and Lymphoid Malignancies

REF 3

ClinicalTrials.gov (NCT03222674) Multi-CAR T Cell Therapy for Acute Myeloid Leukemia

REF 4

Clinical pipeline report, company report or official report of iCell Gene Therapeutics.

REF 5

CLT030, a leukemic stem cell-targeting CLL1 antibody-drug conjugate for treatment of acute myeloid leukemia. Blood Adv. 2018 Jul 24;2(14):1738-1749.

REF 6

ClinicalTrials.gov (NCT04789408) A Phase 1 Open-label, Multicenter Study Evaluating the Safety of KITE-222, an Autologous Anti-CLL-1 CAR T-cell Therapy, in Subjects With Relapsed/Refractory Acute Myeloid Leukemia. U.S.National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT03038230) MCLA-117 in Acute Myelogenous Leukemia. U.S. National Institutes of Health.

REF 8

Off-the-shelf' allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov. 2020 Mar;19(3):185-199.

REF 9

Clinical pipeline report, company report or official report of Cellerant Therapeutics.

REF 10

Clinical pipeline report, company report or official report of Gilead

REF 11

MCLA-117, a CLEC12AxCD3 bispecific antibody targeting a leukaemic stem cell antigen, induces T cell-mediated AML blast lysis. Expert Opin Biol Ther. 2019 Jul;19(7):721-733.

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