Targeting Human C‐Type Lectin‐like Molecule‐1 (CLL1) with a Bispecific Antibody for Immunotherapy of Acute Myeloid Leukemia

Lu, Hua; Zhou, Quan; Deshmukh, V.; Phull, Hardeep; Ma, Jennifer; Tardif, Virginie; Naik, Rahul R.; Bouvard, Claire; Zhang, Yong; Choi, Sei-hyun; Lawson, Brian R.; Zhu, Shoutian; Kim, Chan Hyuk; Schultz, Peter G.

doi:10.1002/anie.201405353

Cited by 67 publications

(45 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consequently, CLEC12A has been proposed as a potential target in the future treatment of AML because residual normal HSCs would be spared. Basic research is currently investigating different approaches in this regard: for example, Lu et al (2014) developed a novel immunotherapeutic bispecific antibody for the recruitment of cytotoxic T‐cells to CLEC12A‐positive AML cells. As mentioned, our results show that CLEC12A does not have the potential of distinguishing CSCs from their normal counterparts in MDS.…”

Section: Discussionmentioning

confidence: 99%

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

et al. 2016

View full text Add to dashboard Cite

SummaryEvidence of distinct disease propagating stem cells in myelodysplastic syndrome (MDS) has emerged in recent years. However, immunophenotypic characterization of these cancer stem cells remains sparse. In acute myeloid leukaemia (AML), we have previously described aberrant expression of the C‐type lectin domain family 12, member A (CLEC12A) as a stable and reliable marker of leukaemia blasts and as a tool for assessing minimal residual disease. Furthermore, CLEC12A has been proposed as a promising marker of leukaemic stem cells in AML. The role of CLEC12A in MDS, however, remains to be elucidated. In this study, we found CLEC12A aberrantly expressed on the CD34+ CD38− cell compartment in 71% (22/31) of MDS patients, distributed across all Revised International Prognostic Scoring System risk groups. We showed that the CD34+ CD38− CLEC12A+ cells were indeed malignant and possessed functional stem cell properties in the long‐term colony‐initiating cell assay. As opposed to reported findings in AML, we showed that cancer stem cells from MDS samples derived from both CLEC12A positive and negative CD34+ CD38− subpopulations. Due to the absence of CLEC12A on normal haematopoietic stem cells, CLEC12A stem cell immunophenotyping may contribute to diagnosing and monitoring MDS patients and could furthermore add knowledge about disease propagating cells in MDS.

show abstract

Section: Discussionmentioning

confidence: 99%

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These nanomicelles were able to display cytotoxicity against leukemic cell lines and primary AML cells, but their activity against LSC, or in in vivo models was not assayed [22]. More recently, a bispecific antibody, αCLL-1-αCD3, was developed: this antibody recruits cytotoxic T cells to CLL-1 positive cells and displays potent and selective cytotoxicity in vitro against several human AML cell lines and primary AML blasts [23]; furthermore, administration of αCLL-1-αCD3 abrogates leukemia development in an U937 AML cell line xenograft model [23].…”

Section: Membrane Markers Of Leukemic Stem Cellsmentioning

confidence: 99%

Targeting LSCs through membrane antigens selectively or preferentially expressed on these cells

Pelosi

Castelli

Testa

2015

Blood Cells, Molecules, and Diseases

View full text Add to dashboard Cite

“…In the setting of malignant haematology, one of the most appealing features of CLEC12A is its lack of expression on CD34 + CD38 − cells in normal bone marrow (BM), regenerating BM and G‐CSF‐stimulated peripheral blood stem cells, making it a potential treatment target. Recent ventures in this regard include the development of anti‐CD3/anti‐CLEC12A bispecific antibodies . The upcoming roles of CLEC12A as a cancer stem cell marker and potential treatment target emphasize the need of knowing the details of its expression pattern on early stem and progenitor cells in healthy individuals.…”

Section: Introductionmentioning

confidence: 99%

Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology

Bill

Niekerk

Woll

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

The C-type lectin domain family 12, member A (CLEC12A) receptor has emerged as a leukaemia-associated and cancer stem cell marker in myeloid malignancies. However, a detailed delineation of its expression in normal haematopoiesis is lacking.Here, we have characterized the expression pattern of CLEC12A on the earliest stem-and myeloid progenitor subsets in normal bone marrow. We demonstrate distinct CLEC12A expression in the classically defined myeloid progenitors, where on to favour non-erythroid colony growth. In conclusion, we provide evidence that the earliest CLEC12A + cell in the haematopoietic tree is the classically defined CMP.Furthermore, we show that CLEC12A-expressing CMPs and MEPs are functionally different than their negative counterparts. Importantly, these data can help determine which cells will be spared during CLEC12A-targeted therapy, and we propose CLEC12A to be included in future studies of myeloid cancer stem cell biology.

show abstract

Targeting Human C‐Type Lectin‐like Molecule‐1 (CLL1) with a Bispecific Antibody for Immunotherapy of Acute Myeloid Leukemia

Cited by 67 publications

References 39 publications

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

Unravelling the relevance of CLEC12A as a cancer stem cell marker in myelodysplastic syndrome

Targeting LSCs through membrane antigens selectively or preferentially expressed on these cells

Mapping the CLEC12A expression on myeloid progenitors in normal bone marrow; implications for understanding CLEC12A‐related cancer stem cell biology

Contact Info

Product

Resources

About