Opening the era of controlled in-vivo Dendritic Cells activation
Designing and developing DC engagers for patients with the toughest cancer or viral infection
EnnoDC I Our Technology
DC engagers
At EnnoDC, we perform controlled in-vivo activation of Dendritic Cells (DC), the master regulator of immunity, with DC engagers.
Each of them is a fully humanized monoclonal antibody which combines:
I A CD40 partial activator [1] head for safe and controlled engagement of DC
I A commutable tail to deliver the selected viral or tumor antigen to the right place
I An engineered IgG4 backbone to avoid FC-related toxicity
After subcutaneous administration, the DC engager primes and activates local DC which induce:
I Activation and proliferation of antigen-specific CD4 and CD8 T-cells
I Activation, proliferation and antibody production of antigen-specific activated B-cells
I Conversion of pro-tumoral M2 macrophages into anti-tumoral M1 macrophages
[1] EnnoDC’s engagers are CD40 partial-agonist antibodies. They recognize CD40 receptors on the surface of DC while blocking CD40 receptor-CD40 ligand interaction to prevent overstimulation and toxicity-related mechanisms
EnnoDC I Immunotherapy
Next generation immunotherapy
01. Well-addressed antigen
The selected antigen is delivered directly to DC: the most powerful Antigen-Presenting Cells of the immune system and the gateway to immune memory.
02. Best DC checkpoint
CD40 (a co-stimulatory receptor which upregulates DC function and play a major role in T and B cells responses) induces superior CD4 and CD8 T-cell stimulation than any other DC receptors.
03. Durable and potent broad immune response
A key feature to overcome tumor and viral immune escape.
04. No collateral damage
Engineered DC engager prevents overstimulation and Fc-related toxicities associated with the old generation of CD40 agonists.
05. Increased therapeutic window
Higher doses for more potent and more durable immune responses.
06. Plug-and-play technology
Improve cost-effectiveness with the same backbone for all DC engagers.
EnnoDC I Mechanism of Action
A targeted and controlled mechanism of action
Loading
DC checkpoint modulator + selected antigen
The selected antigen is loaded onto the tail of the CD40 partial agonist antibody
Delivering
DC engager + Immature DC
The DC engager delivers directly the antigen to DC
Activation
Mature DC
The DC engager activates precisely the DC which process and present the antigen on their surface
Orchestration
T cell and beyond
DC educate CD8 & CD4 cells, boost B-cells proliferation and induce a switch in macrophages identity
EnnoDC I Impact
A broad and durable immune impact
Each DC engager generates long-lived functional specific T and B cells to fight disease and prevent recurrence and reshapes the Tumor Immune Microenvironment to boost local anti-cancer immunity.
CD8 T Cell
Cytotoxic T cell kills directly cancer and virus-infected cells.
CD4 T Cell
Helper T cell activates cytotoxic T cell and prompts B cell to produce antibodies.
B Cell
B cell promotes T cell responses and produces specific antibodies that attack cancer cells, virus and oncogenic virus like HPV.
Macrophages
Pro-tumoral M2 macrophages turn into anti-tumoral M1 macrophages.
EnnoDC I DC Engager Studio
A plug-and-play DC engager studio
EnnoDC has designed and developed a unique DC engager platform that covers from T and B cells epitope mapping (to select the most immunogenic and conserved epitope of the viral or tumor antigen of interest) to clinical POC.
This studio fuels a dynamic pipeline of 5 immunotherapy antibody candidates which help treat solid tumors or virus-induced cancers and prevent viral infections.
EnnoDC I Scientific Publications
Publications
EnnoDC is backed by a team of renowned scientists who regularly publish original research papers, the most relevant of which are accessible below.
Publications feature on websites outside of ennodc.com
View Publications
Preliminary results of a multicentric randomized phase I/IIa trial of an immunotherapy targeting dendritic cells (DC), CD40HVac, in patients with HP16-positive oropharyngeal carcinoma (OPC)
C.Even, A.Wiedemann, A.Aupérin, M.Roulleaux-Dugage, C.Le Tourneau, S. Zurawski, G.Zurawski, C.Bargain, R.Sanchez, M. Codou, H. Savel, M.Centlivre, I.Villa-Languin, A.Abou Lovergne, R. Thiebaut, Y.Levy, P.Gorphe
Poster
ESMO IO 2024 HPVDcVax EnnoDC VRI
A vaccine targeting antigen-presenting cells through CD40 induces protective immunity against Nipah disease
Pastor Y, Reynard O, Iampietro M, Surenaud M, Picard F, El Jahrani N, et al.
Cell Reports Medicine
2024;5:101467.
Refining the DC-targeting vaccination for preventing emerging infectious diseases
Pastor Y, Ghazzaui N, Hammoudi A, Centlivre M, Cardinaud S, Levy Y.
Frontiers in Immunology
2022;13:949779.
Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine
Coléona S, Wiedemanna A, Surénauda M, Lacabaratza C, Huea S, Praguea M, et al.
eBioMedicine, part of THE LANCET Discovery Science
2022;80:104062 .
Anti-CD40 Antibody Fused to CD40 Ligand Is a Superagonist Platform for Adjuvant Intrinsic DC-Targeting Vaccines
Ceglia V, Zurawski S, Montes M, Kroll M, Bouteau A, Wang Z, et al.
Frontiers in Immunology
2022;12:786144.
Targeting SARS-CoV-2 receptor-binding domain to cells expressing CD40 improves protection to infection in convalescent macaques.
Marlin R, Godot V, Cardinaud S, Galhaut M, Coleon S, Zurawski S, et al
Nature Communications
2021;12:5215
TLR9- and CD40-Targeting Vaccination Promotes Human B Cell Maturation and IgG Induction via pDC-Dependent Mechanisms in Humanized Mice
Cheng L, Li G, Pellegry CM, Yasui F, Li F, Zurawski SM, et al.
Frontiers in Immunology
2021;12:672143.
Anti-CD40 Antibodies Fused to CD40 Ligand Have Superagonist Properties
Ceglia V, Zurawski S, Montes M, Bouteau A, Wang Z, Ellis J, et al.
Journal of Immunology
2021;207(8):2060–2076
TLR-9 agonist and CD40-targeting vaccination induces HIV-1 envelope-specific B cells with a diversified immunoglobulin repertoire in humanized mice
Godot V, Tcherakian C, Gil L, Cervera-Marzal I, Li G, Cheng L, et al.
PLoS Pathogens
2020;16(11):e1009025.
Gene Expression Signatures Associated With Immune and Virological Responses to Therapeutic Vaccination With Dendritic Cells in HIV-Infected Individuals
Thiebaut R, Hejblum BP, Hocini H, Bonnabau H, Skinner J, Montes M, et al.
Frontiers in Immunology
2019;10:874.
HIV-1 T cell epitopes targeted to Rhesus macaque CD40 and DCIR: A comparative study of prototype dendritic cell targeting therapeutic vaccine candidates
Flamar AL, Bonnabau H, Zurawski S, Lacabaratz C, Montes M, Richert L, et al.
PloS One
2018;13(11):e0207794.
TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs
Cheng L, Wang Q, Li G, Banga R, Ma J, Yu H, et al.
The Journal of Clinical Investigation
2018;128(10):4387-96.
Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system
Cheng L, Zhang Z, Li G, Li F, Wang L, Zhang L, et al.
Vaccine
2017;35(45):6143-53.
Superiority in Rhesus Macaques of Targeting HIV-1 Env gp140 to CD40 versus LOX-1 in Combination with Replication-Competent NYVAC-KC for Induction of Env-Specific Antibody and T Cell Responses
Zurawski G, Shen X, Zurawski S, Tomaras GD, Montefiori DC, Roederer M, et al.
Journal of Virology
2017;91(9).
Targeting HIV-1 Env gp140 to LOX-1 Elicits Immune Responses in Rhesus Macaques
Zurawski G, Zurawski S, Flamar AL, Richert L, Wagner R, Tomaras GD, et al.
PloS One
2016;11(4):e0153484.
Functional Specialty of CD40 and Dendritic Cell Surface Lectins for Exogenous Antigen Presentation to CD8(+) and CD4(+) T Cells
Yin W, Gorvel L, Zurawski S, Li D, Ni L, Duluc D, et al.
The Lancet
2016;5:46-58.
Therapeutic HPV Cancer Vaccine Targeted to CD40 Elicits Effective CD8+ T-cell Immunity
Yin W, Duluc D, Joo H, Xue Y, Gu C, Wang Z, et al.
Cancer Immunology Research
2016;4(10):823-34.
Targeting dendritic cells in humanized mice receiving adoptive T cells via monoclonal antibodies fused to Flu epitopes
Graham JP, Authie P, Yu CI, Zurawski SM, Li XH, Marches F, et al.
Vaccine
2016;34(41):4857-65.
Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses In Vivo
Flamar AL, Contreras V, Zurawski S, Montes M, Dereuddre-Bosquet N, Martinon F, et al.
PloS One
2015;10(9):e0135513.
Dendritic cell-based therapeutic vaccine elicits polyfunctional HIV-specific T-cell immunity associated with control of viral load
Levy Y, Thiebaut R, Montes M, Lacabaratz C, Sloan L, King B, et al.
European Journal of Immunology
2014;44(9):2802-10.
C-type lectin-like receptor LOX-1 promotes dendritic cell-mediated class-switched B cell responses
Joo H, Li D, Dullaers M, Kim TW, Duluc D, Upchurch K, et al.
Immunity
2014;41(4):592-604.
Targeting concatenated HIV antigens to human CD40 expands a broad repertoire of multifunctional CD4+ and CD8+ T cells
Flamar AL, Xue Y, Zurawski SM, Montes M, King B, Sloan L, et al.
Aids
2013;27(13):2041-51.
Noncovalent assembly of anti-dendritic cell antibodies and antigens for evoking immune responses in vitro and in vivo
Flamar AL, Zurawski S, Scholz F, Gayet I, Ni L, Li XH, et al.
Journal of Immunology
2012;189(5):2645-55.
Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10–producing suppressive CD4+ T cells
Li D, Romain G, Flamar AL, Duluc D, Dullaers M, Li XH, et al.
