Selective tumor antigen vaccine delivery to human CD169
            <sup>+</sup>
            antigen-presenting cells using ganglioside-liposomes

Affandi, Alsya J.; Grabowska, Joanna; Olesek, Katarzyna; Venegas, Miguel Lopez; Barbaria, Arnaud; Rodríguez, Elizabeth; Mulder, Patrick P. G.; Pijffers, Helen J; Ambrosini, Martino; Kalay, Hakan; O’Toole, Tom; Zwart, E.; Kazemier, Geert; Nazmi, Kamran; Bikker, Floris J.; Stöckl, Johannes; Eertwegh, Alfons J.M. van den; Gruijl, Tanja D. de; Storm, Gert; Kooyk, Yvette van; Haan, Joke M. M. den

doi:10.1073/pnas.2006186117

Cited by 62 publications

(55 citation statements)

References 82 publications

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“…In addition, a new subset of human DCs, characterized by the expression of Axl and Siglec-6 (AS DC), was also shown to express CD169 [46]. We recently demonstrated that ganglioside-containing liposomes can be used to selectively target and activate these human AS DCs in a CD169-dependent manner [47]. In this study, we have optimized targeting to human and murine cells and show that the liposomal incorporation of either 3 or 5 mol% GM3 led to strong and specific binding to CD169-expressing cells in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages

et al. 2020

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Despite promising progress in cancer vaccination, therapeutic effectiveness is often insufficient. Cancer vaccine effectiveness could be enhanced by targeting vaccine antigens to antigen-presenting cells, thereby increasing T-cell activation. CD169-expressing splenic macrophages efficiently capture particulate antigens from the blood and transfer these antigens to dendritic cells for the activation of CD8+ T cells. In this study, we incorporated a physiological ligand for CD169, the ganglioside GM3, into liposomes to enhance liposome uptake by CD169+ macrophages. We assessed how variation in the amount of GM3, surface-attached PEG and liposomal size affected the binding to, and uptake by, CD169+ macrophages in vitro and in vivo. As a proof of concept, we prepared GM3-targeted liposomes containing a long synthetic ovalbumin peptide and tested the capacity of these liposomes to induce CD8+ and CD4+ T-cell responses compared to control liposomes or soluble peptide. The data indicate that the delivery of liposomes to splenic CD169+ macrophages can be optimized by the selection of liposomal constituents and liposomal size. Moreover, optimized GM3-mediated liposomal targeting to CD169+ macrophages induces potent immune responses and therefore presents as an interesting delivery strategy for cancer vaccination.

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Section: Discussionmentioning

confidence: 99%

Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages

et al. 2020

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“…While most Siglecs confer tolerogenic responses, the Siglec-1 (or CD169) receptor, expressed on splenic macrophages is of special interest for anti-tumor responses. These cells transferred antigen to cross-presenting cDC1s when targeted with liposomes coated with the Siglec-1 ligand GM3, conferring beneficial anti-tumor CD8+ T cell responses ( 115 ). FcR, which bind to the constant domains of antibodies can be targeted by coating liposomes with antibodies.…”

Section: Battling Cancer With DC Targeted Liposome Vaccinesmentioning

confidence: 99%

Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance

Nagy

Haas²,

Geijtenbeek³

et al. 2021

Front. Immunol.

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Dendritic cells (DCs) are paramount in initiating and guiding immunity towards a state of activation or tolerance. This bidirectional capacity of DCs sets them at the center stage for treatment of cancer and autoimmune or allergic conditions. Accordingly, many clinical studies use ex vivo DC vaccination as a strategy to boost anti-tumor immunity or to suppress immunity by including vitamin D3, NF-κB inhibitors or retinoic acid to create tolerogenic DCs. As harvesting DCs from patients and differentiating these cells in vitro is a costly and cumbersome process, in vivo targeting of DCs has huge potential as nanoparticulate platforms equipped with activating or tolerogenic adjuvants can modulate DCs in their natural environment. There is a rapid expansion of the choices of nanoparticles and activation- or tolerance-promoting adjuvants for a therapeutic vaccine platform. In this review we highlight the most recent nanomedical approaches aimed at inducing immune activation or tolerance via targeting DCs, together with novel fundamental insights into the mechanisms inherent to fostering anti-tumor or tolerogenic immunity.

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“…The authors used the natural ligands of CD169, gangliosides, as targeting ligands and constructed liposomal vaccine carriers to deliver TAs. Through targeted co-delivery of TA and TLR ligand to CD169 + monocyte-derived DCs and AXL + CD169 + DCs, the ganglioside-liposomes induce robust cross-presentation and activation of TA-specific CD8 + T cells 66 . Rajpu et al engineered polymeric nanovaccines using inulin acetate (InAc) as the polymer material.…”

Section: Antigen Release and Presentationmentioning

confidence: 99%

Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?

Zuo¹,

Song²,

Zhang³

et al. 2021

Theranostics

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Immunotherapy provides a new avenue for combating cancer. Current research in anticancer immunotherapy is primary based on T cell-mediated cellular immunity, which can be divided into seven steps and is named the cancer-immunity cycle. Unfortunately, clinical applications of cancer immunotherapies are restricted by inefficient drug delivery, low response rates, and unmanageable adverse reactions. In response to these challenges, the combination of nanotechnology and immunotherapy (nano-immunotherapy) has been extensively studied in recent years. Rational design of advanced nano-immunotherapies requires in-depth consideration of “which” immune step is targeted, “why” it needs to be further enhanced, and “what” nanotechnology can do for immunotherapy. However, the applications and effects of nanotechnology in the cancer-immunity cycle have not been well reviewed. Herein, we summarize the current developments in nano-immunotherapy for each stage of cancer cellular immunity, with special attention on the which, why and what. Furthermore, we summarize the advantages of nanotechnology for combination immunotherapy in two categories: enhanced efficacy and reduced toxicity. Finally, we discuss the challenges of nano-immunotherapy in detail and provide a perspective.

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Selective tumor antigen vaccine delivery to human CD169 ⁺ antigen-presenting cells using ganglioside-liposomes

Cited by 62 publications

References 82 publications

Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages

Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages

Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance

Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?

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Selective tumor antigen vaccine delivery to human CD169 + antigen-presenting cells using ganglioside-liposomes

Cited by 62 publications

References 82 publications

Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages

Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages

Therapeutic Liposomal Vaccines for Dendritic Cell Activation or Tolerance

Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?

Contact Info

Product

Resources

About

Selective tumor antigen vaccine delivery to human CD169 ⁺ antigen-presenting cells using ganglioside-liposomes