Last update 19 Sep 2024

CLEC9A

Last update 19 Sep 2024

Basic Info

Synonyms

C-type lectin domain containing 9A, C-type lectin domain family 9 member A, CD370

+ [4]

Introduction

Functions as an endocytic receptor on a small subset of myeloid cells specialized for the uptake and processing of material from dead cells. Recognizes filamentous form of actin in association with particular actin-binding domains of cytoskeletal proteins, including spectrin, exposed when cell membranes are damaged, and mediate the cross-presentation of dead-cell associated antigens in a Syk-dependent manner.

Drugs associated with CLEC9A

Anti-CLEC9A antibody(Monash University/University of Queensland)

Target

CLEC9A

Mechanism

CLEC9A modulators

Active Org.

The University of Queensland [+1]

Originator Org.

The University of Queensland [+1]

Active Indication

Infectious Diseases [+2]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CLEC9A

100 Translational Medicine associated with CLEC9A

0 Patents (Medical) associated with CLEC9A

196

Literatures (Medical) associated with CLEC9A

01 Sep 2024·Immunobiology

Synthetic hemozoin as a nanocarrier for cross-presentation

Article

Author: Augusto, Leonardo ; do Amaral, Jônatas Bussador ; Souza, Rebeca Santana ; Torres-Dias, Letícia ; Bachi, André Luis Lacerda ; Shio, Marina Tiemi ; Moreira, Jessica Carolina Alves ; Paggi, Douglas de Oliveira

It is known that conventional antigen presentation involves phagocytosis of antigens followed by its internalization in endocytic compartments and presentation of epitopes through MHC class II molecules for CD4 T cells. However, since 1976 a cross-presentation pathway has been studied, in which CD8 T cells are activated via MHC class I with antigens acquired through phagocytosis or endocytosis by dendritic cells (DCs). Among some important molecules involved in the cross-presentation, the C-type lectin receptor of the Dectin-1 cluster (CLECs), particularly the CLEC9A receptor, not only is expressed in dendritic cells but also presents a pivotal role in this context. In special, CLEC12A has been highlighted as a malaria pigment hemozoin (HZ) receptor. During Plasmodium infection, hemozoin crystals defend the parasite against heme toxicity within erythrocytes, as well as the released native HZ elicits pro-inflammatory responses and can induce cross-presentation. Particularly, this crystal can be synthesized from hematin anhydride and mimics the native form, and the gaps generated between the nanocrystal domains during its synthesis allow for substance coupling followed by its coating. Therefore, this study aimed to assess whether synthetic hemozoin (sHz) or hematin anhydride could be a nanocarrier and promote cross-presentation in dendritic cells. Firstly, it was verified that sHz can carry coated and coupled antigens, the compounds can associate to LAMP1-positive vesicles and decrease overall intracellular pH, which can potentially enhance the cross-presentation of ovalbumin and Leishmania infantum antigens. Thus, this study adds important data in the molecular intricacies of antigen presentation by showing not only the sHz immunomodulatory properties but also its potential applications as an antigen carrier.

01 Jul 2024·Molecular Therapy

Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice

Article

Author: Tan, Yee Joo ; Caminschi, Irina ; Cheang, Nicholas You Zhi ; Yeoh, Aileen Ying-Yan ; Chua, Benson Yen Leong ; Lahoud, Mireille Hanna ; Tay, Douglas Jie Wen ; Tan, Caris Qi Hui ; Macary, Paul Anthony ; Tullett, Kirsteen McInnes ; Yap, Wee Chee ; Chen, Huixin ; Purushotorma, Kiren ; Tan, Chee Wah ; Alonso, Sylvie ; Tan, Peck Szee ; Qian, Xinlei ; Tan, Kai Sen

Current coronavirus disease 2019 vaccines face limitations including waning immunity, immune escape by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, limited cellular response, and poor mucosal immunity. We engineered a Clec9A-receptor binding domain (RBD) antibody construct that delivers the SARS-CoV-2 RBD to conventional type 1 dendritic cells. Compared with non-targeting approaches, single dose immunization in mice with Clec9A-RBD induced far higher RBD-specific antibody titers that were sustained for up to 21 months after vaccination. Uniquely, increasing neutralizing and antibody-dependent cytotoxicity activities across the sarbecovirus family was observed, suggesting antibody affinity maturation over time. Consistently and remarkably, RBD-specific follicular T helper cells and germinal center B cells persisted up to 12 months after immunization. Furthermore, Clec9A-RBD immunization induced a durable mono- and poly-functional T-helper 1-biased cellular response that was strongly cross-reactive against SARS-CoV-2 variants of concern, including Omicron subvariants, and with a robust CD8⁺ T cell signature. Uniquely, Clec9A-RBD single-shot systemic immunization effectively primed RBD-specific cellular and humoral immunity in lung and resulted in significant protection against homologous SARS-CoV-2 challenge as evidenced by limited body weight loss and approximately 2 log₁₀ decrease in lung viral loads compared with non-immunized controls. Therefore, Clec9A-RBD immunization has the potential to trigger robust and sustained, systemic and mucosal protective immunity against rapidly evolving SARS-CoV2 variants.

01 Jun 2024·Immunity, Inflammation and Disease

Exploring the prognostic significance of immunogenic cell death‐related genes as risk biomarkers in cervical cancer

Article

Author: Jin, Shuangmei ; Chen, Jingdong

AbstractBackgroundImmunogenic cell death (ICD) is a process in which dying cells stimulate an immune response. It is a regulated form of cell death that can remodel the tumor microenvironment (TME) and activate the immune system, making immunotherapy more effective. This work was designed to identify prognostic gene features associated with ICD in cervical cancer (CC).MethodsBased on CC datasets and a set of ICD‐related genes obtained from public databases, we first filtered out ICD‐related genes unrelated to CC survival using univariate analysis. Subsequently, LASSO regression and multivariate Cox regression analysis were employed to develop prognostic feature genes based on ICD. For the construction and validation of the model, eight genes (CXCL1, IL1B, TNF, YKT6, PDIA3, ROCK1, CXCR3, and CLEC9A) were chosen. A nomogram was created to forecast the prognosis of CC individuals, and Kaplan–Meier curves were utilized to explore the survival disparities among different risk groups of CC individuals.ResultsssGSEA analysis was employed to investigate immune differences between two risk groups, revealing that the low‐risk group exhibited elevated levels of immune cell infiltration, enhanced activation of immune function, and a higher immunophenoscore compared with the other group, which highlighted the relevance of ICD to TME.ConclusionWe constructed a prognostic model based on genetic biomarkers of ICD for prognostic prediction of CC patients. Our model demonstrated excellent discriminative and calibration capabilities, providing a valuable tool for prognostic prediction and assessing the potential efficacy of immunotherapy in CC.

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CLEC9A

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