Cationic Liposomes: A Flexible Vaccine Delivery System for Physicochemically Diverse Antigenic Peptides

Heuts, Jeroen; Varypataki, Eleni Maria; Maaden, Koen van der; Romeijn, Stefan; Drijfhout, Jan W.; Scheltinga, Anton Terwisscha van; Ossendorp, Ferry; Jiskoot, Wim

doi:10.1007/s11095-018-2490-6

Cited by 52 publications

(52 citation statements)

References 20 publications

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“…This aspect is not trivial in classical peptidebased systems, as amino acid sequence dictates the physicochemical properties of the vaccine, adding complications to the manufacturing process and formulation. 6 In short, an ideal neoantigen vaccine platform should be flexible enough to be able to incorporate a multitude of epitopes and allow fast and reliable production independently of the exact amino acid sequences of the selected epitopes.…”

Section: Introductionmentioning

confidence: 99%

A poly-neoantigen DNA vaccine synergizes with PD-1 blockade to induce T cell-mediated tumor control

Tondini

Arakelian

Oosterhuis³

et al. 2019

OncoImmunology

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The combination of immune-stimulating strategies has the potency to improve immunotherapy of cancer. Vaccination against neoepitopes derived from patient tumor material can generate tumorspecific T cell immunity, which could reinforce the efficacy of checkpoint inhibitor therapies such as anti-PD-1 treatment. DNA vaccination is a versatile platform that allows the inclusion of multiple neoantigencoding sequences in a single formulation and therefore represents an ideal platform for neoantigen vaccination. We developed an anti-tumor vaccine based on a synthetic DNA vector designed to contain multiple cancer-specific epitopes in tandem. The DNA vector encoded a fusion gene consisting of three neoepitopes derived from the mouse colorectal tumor MC38 and their natural flanking sequences as 40 amino acid stretches. In addition, we incorporated as reporter epitopes the helper and CTL epitope sequences of ovalbumin. The poly-neoantigen DNA vaccine elicited T cell responses to all three neoantigens and induced functional CD8 and CD4 T cell responses to the reporter antigen ovalbumin after intradermal injection in mice. The DNA vaccine was effective in preventing outgrowth of B16 melanoma expressing ovalbumin in a prophylactic setting. Moreover, the combination of therapeutic DNA vaccination and anti-PD-1 treatment was synergistic in controlling MC38 tumor growth whereas individual treatments did not succeed. These data demonstrate the potential of DNA vaccination to target multiple neoepitopes in a single formulation and highlight the cooperation between vaccinebased and checkpoint blockade immunotherapies for the successful eradication of established tumors.

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Section: Introductionmentioning

confidence: 99%

A poly-neoantigen DNA vaccine synergizes with PD-1 blockade to induce T cell-mediated tumor control

Tondini

Arakelian

Oosterhuis³

et al. 2019

OncoImmunology

Self Cite

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“…Importantly, a considerable number of T helper cell peptides relevant to the clinical translation of our liposome-based vaccine (e.g., those derived from tetanus toxoid or licensed vaccines against hepatitis B virus (HBV)) are less hydrophilic than the model peptide employed in the present study. In fact, many are hydrophobic and it is expected that their formulation is not or considerably less affected by the presence/absence of charged lipids [ 44 , 78 ].…”

Section: Resultsmentioning

confidence: 99%

Conjugation of Native-Like HIV-1 Envelope Trimers onto Liposomes Using EDC/Sulfo-NHS Chemistry: Requirements and Limitations

et al. 2020

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The display of native-like human immunodeficiency virus type 1 envelope (HIV-1 Env) trimers on liposomes has gained wide attention over the last few years. Currently, available methods have enabled the preparation of Env-liposome conjugates of unprecedented quality. However, these protocols require the Env trimer to be tagged and/or to carry a specific functional group. For this reason, we have investigated N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide/N-Hydroxysulfosuccinimide (EDC/Sulfo-NHS) chemistry for its potential to covalently conjugate tag-free, non-functionalized native-like Env trimers onto the surface of carboxyl-functionalized liposomes. The preservation of the liposome’s physical integrity and the immunogen’s conformation required a fine-tuned two-step approach based on the controlled use of β-mercaptoethanol. The display of Env trimers was strictly limited to activated liposomes of positive charge, i.e., liposomes with a positive zeta potential that carry amine-reactive Sulfo-NHS esters on their surface. In agreement with that, conjugation was found to be highly ionic strength- and pH-dependent. Overall, we have identified electrostatic pre-concentration (i.e., close proximity between negatively charged Env trimers and positively charged liposomes established through electrostatic attraction) to be crucial for conjugation reactions to proceed. The present study highlights the requirements and limitations of potentially scalable EDC/Sulfo-NHS-based approaches and represents a solid basis for further research into the controlled conjugation of tag-free, non-functionalized native-like Env trimers on the surface of liposomes, and other nanoparticles.

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“…Heuts et al developed three liposome formulations to encapsulate 15 different long synthetic peptides (LSPs). The peptide containing the OVA SIINFEKL epitope was encapsulated in DOTAP:DOPC (dioleoyl-3-trimethylammonium propane:dioleyl phosphatidylcholine) liposome using three solvents and all three formulations were shown to activate CD8 + T-cells and antigen presentation by dendritic cells, suggesting the potential of such liposomes as delivery system for personalized cancer vaccines [19] ( Table 1).…”

Section: Liposomementioning

confidence: 99%

Nanoparticles to Improve the Efficacy of Peptide-Based Cancer Vaccines

Tornesello

Tagliamonte

Tornesello

et al. 2020

Cancers

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Nanoparticles represent a potent antigen presentation and delivery system to elicit an optimal immune response by effector cells targeting tumor-associated antigens expressed by cancer cells. Many types of nanoparticles have been developed, such as polymeric complexes, liposomes, micelles and protein-based structures such as virus like particles. All of them show promising results for immunotherapy approaches. In particular, the immunogenicity of peptide-based cancer vaccines can be significantly potentiated by nanoparticles. Indeed, nanoparticles are able to enhance the targeting of antigen-presenting cells (APCs) and trigger cytokine production for optimal T cell response. The present review summarizes the categories of nanoparticles and peptide cancer vaccines which are currently under pre-clinical evaluation.

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Cationic Liposomes: A Flexible Vaccine Delivery System for Physicochemically Diverse Antigenic Peptides

Cited by 52 publications

References 20 publications

A poly-neoantigen DNA vaccine synergizes with PD-1 blockade to induce T cell-mediated tumor control

A poly-neoantigen DNA vaccine synergizes with PD-1 blockade to induce T cell-mediated tumor control

Conjugation of Native-Like HIV-1 Envelope Trimers onto Liposomes Using EDC/Sulfo-NHS Chemistry: Requirements and Limitations

Nanoparticles to Improve the Efficacy of Peptide-Based Cancer Vaccines

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