Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy

Zeng, Bijun; Middelberg, Anton P. J.; Gemiarto, Adrian Tandhyka; MacDonald, Kelli P. A.; Baxter, Alan G.; Talekar, Meghna; Moi, Davide; Tullett, Kirsteen M.; Caminschi, Irina; Lahoud, Mireille H.; Mazzieri, Roberta; Dolcetti, Riccardo; Thomas, Ranjeny

doi:10.1172/jci96791

Cited by 76 publications

(63 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, an improved understanding of the disease mechanisms will enable the development of more efficient nanomedicines with mechanisms of action beyond tumor nanoparticle accumulation [19,20]. For instance, nanoparticles are currently being explored in the fields of adoptive cell therapy and immune modulation in various stages of preclinical and clinical development [21]. Moreover, recent preclinical studies and clinical trials have shown benefits of combination therapies, and particularly, the ability of nanoparticles to simultaneously deliver therapeutic agents, such as small molecules, genetic material, and biologics [22].…”

mentioning

confidence: 99%

The solid progress of nanomedicine

Martins

Neves

Fuente

et al. 2020

Drug Deliv. and Transl. Res.

102

View full text Add to dashboard Cite

show abstract

mentioning

confidence: 99%

The solid progress of nanomedicine

Martins

Neves

Fuente

et al. 2020

Drug Deliv. and Transl. Res.

102

View full text Add to dashboard Cite

show abstract

“…Recent preclinical studies and clinical trials combined the use of DC stimulators with the growth factor FMS-like tyrosine kinase-3 ligand (FLT3L) to increase DC numbers in peripheral blood [59,60]. For optimal delivery, the adjuvants can be encapsulated in nanoparticles, liposomes, or immunostimulatory complexes specifically targeting DCs [61][62][63], whereas to guarantee a sufficient availability of immunogenic TAAs, in situ vaccination can be combined with ICD-inducing therapeutic modalities, such as doxorubicine or radiotherapy.…”

Section: In Situ Vaccinationmentioning

confidence: 99%

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

et al. 2020

View full text Add to dashboard Cite

The safety and feasibility of dendritic cell (DC)-based immunotherapies in cancer management have been well documented after more than twenty-five years of experimentation, and, by now, undeniably accepted. On the other hand, it is equally evident that DC-based vaccination as monotherapy did not achieve the clinical benefits that were predicted in a number of promising preclinical studies. The current availability of several immune modulatory and targeting approaches opens the way to many potential therapeutic combinations. In particular, the evidence that the immune-related effects that are elicited by immunogenic cell death (ICD)-inducing therapies are strictly associated with DC engagement and activation strongly support the combination of ICD-inducing and DC-based immunotherapies. In this review, we examine the data in recent studies employing tumor cells, killed through ICD induction, in the formulation of anticancer DC-based vaccines. In addition, we discuss the opportunity to combine pharmacologic or physical therapeutic approaches that can promote ICD in vivo with in situ DC vaccination.

show abstract

“…Alternatively, specific peptides selected by in vitro evolution systems and beads coated with a synthetic F-actin/myosin II complex can be used for in vivo targeting of antigens toward DNGR-1 (23,24). Moreover, anti-DNGR-1 antibodies can be used to deliver antigen-containing nanoemulsions with immunostimulatory properties (25). Upon engagement with F-actin or monoclonal antibodies, surface DNGR-1 is internalized (10) and directed to non-degradative endosomal compartments (8), which are associated with enhanced antigen cross-presentation (26).…”

Section: Dngr-1 As a Targetable Cdc1 Markermentioning

confidence: 99%

DNGR-1, a Dendritic Cell-Specific Sensor of Tissue Damage That Dually Modulates Immunity and Inflammation

2020

View full text Add to dashboard Cite

DNGR-1 (encoded by CLEC9A) is a C-type lectin receptor (CLR) with an expression profile that is mainly restricted to type 1 conventional dendritic cells (cDC1s) both in mice and humans. This delimited expression pattern makes it appropriate for defining a cDC1 signature and for therapeutic targeting of this population, promoting immunity in mouse models. Functionally, DNGR-1 binds F-actin, which is confined within the intracellular space in healthy cells, but is exposed when plasma membrane integrity is compromised, as happens in necrosis. Upon F-actin binding, DNGR-1 signals through SYK and mediates cross-presentation of dead cell-associated antigens. Cross-presentation to CD8 + T cells promoted by DNGR-1 during viral infections is key for cross-priming tissue-resident memory precursors in the lymph node. However, in contrast to other closely related CLRs such as Dectin-1, DNGR-1 does not activate NFκB. Instead, recent findings show that DNGR-1 can activate SHP-1 to limit inflammation triggered by heterologous receptors, which results in reduced production of inflammatory chemokines and neutrophil recruitment into damaged tissues in both sterile and infectious processes. Hence, DNGR-1 reduces immunopathology associated with tissue damage, promoting disease tolerance to safeguard tissue integrity. How DNGR-1 signals are conditioned by the microenvironment and the detailed molecular mechanisms underlying DNGR-1 function have not been elucidated. Here, we review the expression pattern and structural features of DNGR-1, and the biological relevance of the detection of tissue damage through this CLR.

show abstract

Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy

Cited by 76 publications

References 62 publications

The solid progress of nanomedicine

The solid progress of nanomedicine

Dendritic Cells and Immunogenic Cancer Cell Death: A Combination for Improving Antitumor Immunity

DNGR-1, a Dendritic Cell-Specific Sensor of Tissue Damage That Dually Modulates Immunity and Inflammation

Contact Info

Product

Resources

About