Vaccination with dendritic cells pulsed ex vivo with gp100 peptide-decorated liposomes enhances the efficacy of anti PD-1 therapy in a mouse model of melanoma

Yazdani, Mona; Gholizadeh, Zahra; Nikpoor, Amin Reza; Hatamipour, Mahdi; Alani, Behrang; Nikzad, Hossein; Roshan, Nema Mohamadian; Jaafari, Mahmoud Reza; Noureddini, Mahdi; Badiee, Ali

doi:10.1016/j.vaccine.2020.06.055

Cited by 15 publications

(12 citation statements)

References 48 publications

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“…It is worth mentioning that the amount of antigen we used for immunizations (2.86 µg/dose) was set to be close to the minimum dose that was needed to trigger T cell proliferation in vitro 19 . On the other hand, in preclinical vaccination studies, higher amounts of CpG-ODN were usually used to elicit a solid immune response 27 , 28 .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have proved that liposomes are an effective delivery vehicle that could improve the CpG-ODN half-life and increase Th1 immune responses 31 . We used a cationic lipid, DOTAP, in the liposomal formulation and then conjugated gp100 peptides to the surface of liposomes as previously described in details 19 . DOTAP was more effective in enhancing CpG-ODN mediated immunity attributed to electrostatic interactions between the positively charged DOTAP and the negatively charged CpG-ODN 32 .…”

Section: Discussionmentioning

confidence: 99%

“…DC-based vaccine preparation. Cationic liposomes (DOTAP: Chol) were prepared by thin lipid film hydration method, and then the gp100 peptide was conjugated to them as was utterly explained in our previous study 19 . For those treatment groups containing CpG-ODN, CpG-ODN was mixed with liposomal or non-liposomal gp100 and left for 30 min at room temperature before taken up by DCs (ratio of CpG-ODN per total lipid: 0.002 µmol per 0.24 µmol) 27 .…”

Section: Methodsmentioning

confidence: 99%

“…Murine BM progenitor cells were used for DCs preparation according to the previously described method 19 , 39 and characterized for maturation state. 5 × 10 5 matured DCs (by LPS) (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…We evaluated the role of liposomal peptide delivery to dendritic cells and their use as DC vaccine in our previous study in which the significant efficacy of liposomal peptide pulsed DC vaccination in the enhancement of PD-1 blockade therapy was proved 19 . However, in this study, we investigated the role of CpG-OGN co-delivered with liposomal or non-liposomal peptide to ex vivo generated DCs as an anti-cancer vaccine in combination with PD-1 blockade therapy.…”

Section: Introductionmentioning

confidence: 99%

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Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy

Yazdani

Gholizadeh

Nikpoor

et al. 2021

Sci Rep

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Lack of pre-existing tumor infiltrated T cells resulting in resistance to programmed cell death protein 1 (PD-1) blockade therapies can be solved by combining with anti-cancer vaccines and CpG-ODN in increasing T cell expansion and infiltration. Therefore, we prepared an ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of either liposomal or non-liposomal gp100 antigen (2.8 µg) plus CpG-ODN (800 ng) formulations and evaluated its anti-tumor activity in combination with anti-PD-1 therapy. Our results showed a combination of liposomal peptide plus CpG-ODN pulsed DC with anti-PD-1 antibody was more efficacious, as evidenced by a significant increase in Teff/Treg TILs with a marked fourfold elevation of IFN-γ expression level in the tumor site of treated mice which reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. Furthermore, this combination also led to a remarkable tumor remission and prolonged survival rate in melanoma-bearing mice compared to non-liposomal peptide plus CpG-ODN or single-treated liposomal peptide formulations. Our results provide essential insights to devise combining regimens to improve the efficacy of immune checkpoint blockers even by a low dose of peptide and CpG-ODN.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Murine BM progenitor cells were used for DCs preparation according to the previously described method 19 , 39 and characterized for maturation state. 5 × 10 5 matured DCs (by LPS) (Fig.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy

Yazdani

Gholizadeh

Nikpoor

et al. 2021

Sci Rep

Self Cite

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New advances in pharmaceutical strategies for sensitizing anti‐PD‐1 immunotherapy and clinical research

Jiang

Qin

et al. 2022

WIREs Nanomed Nanobiotechnol

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Attempts have been made continuously to use nano-drug delivery system (NDDS) to improve the effect of antitumor therapy. In recent years, especially in the application of immunotherapy represented by antiprogrammed death receptor 1 (anti-PD-1), it has been vigorously developed. Nanodelivery systems are significantly superior in a number of aspects including increasing the solubility of insoluble drugs, enhancing their targeting ability, prolonging their half-life, and reducing side effects. It can not only directly improve the efficacy of anti-PD-1 immunotherapy, but also indirectly enhance the antineoplastic efficacy of immunotherapy by boosting the effectiveness of therapeutic modalities such as chemotherapy, radiotherapy, photothermal, and photodynamic therapy (PTT/PDT). Here, we summarize the studies published in recent years on the use of nanotechnology in pharmaceutics to improve the efficacy of anti-PD-1 antibodies, analyze their characteristics and shortcomings, and combine with the current clinical research on anti-PD-1 antibodies to provide a reference for the design of future nanocarriers, so as to further expand the clinical application prospects of NDDSs.

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Tumour-derived extracellular vesicle based vaccines for melanoma treatment

Gonzalez-Melero

Hernández

Santos‐Vizcaíno

et al. 2023

Drug Deliv. and Transl. Res.

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The interest of extracellular vesicles (EVs) in cancer immunotherapy is increasing every day. EVs are lipid bilayer vesicles released by most cells, which contain the molecular signature of their parent cell. Melanoma-derived EVs present antigens specific to this aggressive type of cancer, but they also exert immunomodulatory and pro-metastatic activity. Until now, most reviews focus on the immunoevasive characteristics of tumour-derived EVs, but do not help to overcome the issues related to them. In this review, we describe isolation methods of EVs from melanoma patients and most interesting markers to oversee their effect if they are used as antigen carriers. We also discuss the methods developed so far to overcome the lack of immunogenicity of melanoma-derived EVs, which includes EV modification or adjuvant co-administration. In summary, we conclude that EVs can be an interesting antigen source for immunotherapy development once EV obtaining is optimised and the understanding of the mechanisms behind their multiple effects is further understood. Graphical Abstract

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Vaccination with dendritic cells pulsed ex vivo with gp100 peptide-decorated liposomes enhances the efficacy of anti PD-1 therapy in a mouse model of melanoma

Cited by 15 publications

References 48 publications

Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy

Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy

New advances in pharmaceutical strategies for sensitizing anti‐PD‐1 immunotherapy and clinical research

Tumour-derived extracellular vesicle based vaccines for melanoma treatment

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