A modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity

Das, Krishna; Belnoue, Elodie; Rossi, Matteo A. C.; Hofer, Tamara; Danklmaier, Sarah; Nolden, Tobias; Schreiber, Liesa-Marie; Angerer, K. Von; Kimpel, Janine; Hoegler, S.; Spiesschaert, Bart; Kenner, Lukas; Laer, Dorothee von; Elbers, Knut; Derouazi, Madiha; Wollmann, Guido

doi:10.1038/s41467-021-25506-6

Cited by 37 publications

(43 citation statements)

References 50 publications

(71 reference statements)

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“…TC-1 tumor cells provided by T.C. Wu (Johns Hopkins University, Maryland, USA) and MC-38 tumor cells (kindly gifted from Gottfried Baier; Medical University of Innsbruck, Innsbruck, Austria) were cultured and implanted as previously described [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Recombinant protein vaccine KISIMA constructs were produced as described [ 2 ]. VSV-GP-HPV and KISIMA-Mad25 have been described previously and contain either full-length proteins or epitopes of the HPV-E2, -E6 and E7 proteins [ 12 ]. The KISIMA-Mad46 peptide vaccine was generated de novo as described previously [ 2 ] and consisted of a CPP, a Mad containing three different MC-38-specific neo-antigens (Adpgk, Reps1 [ 13 ] and Rpl18 [ 14 ]) and a TLR2/4 agonist.…”

Section: Methodsmentioning

confidence: 99%

“…In short, the peptide sequence of KISIMA-Mad46 was back-translated, codon-optimized for mus musculus and cloned into position 5 of the VSV-GP genome. All viruses were rescued and produced as described in [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…with 10 7 TCID 50 VSV-GP. Vaccination schedules for the respective tumor models were performed as described [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Compared to the respective homologous vaccination regimen, the prime-boost combination strongly enhanced the quantities and qualities of antigen-specific cytotoxic T cells (CTLs) while also remodeling the tumor microenvironment (TME) towards a pro-inflammatory composition. Furthermore, targeting PD-1/PDL-1 interaction further increased the anti-tumoral efficacy of the heterologous prime-boost vaccination [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Hofer

Rossi

Carboni

et al. 2021

Cancers

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Heterologous prime-boost settings with a protein vaccine and the viral vector vesicular stomatitis virus, both expressing tumor-associated antigens (KISIMA-TAA and VSV-GP-TAA), have been previously shown to generate potent antitumor immunity. In the cold TC-1 model (HPV antigen) and the immune-infiltrate MC-38 model (Adpgk, Reps1 and Rpl18 neo-antigens), we further investigated pivotal immune cells that educate CD8+ T cells. Heterologous prime-boost vaccination induced a superior antitumor response characterized by the increase in number and functionality of antigen-specific CD8+ T cells, recruitment of cross-presenting dendritic cells, and polarization of CD4+ T cells towards an antitumor Th1 phenotype within the tumor and tumor-draining lymph nodes, turning the cold TC-1 tumor into a hot, inflamed tumor. In the inflamed MC-38 tumor model, treatment combination markedly prolonged the overall survival of mice. Treatment with multi-epitope vaccines also induced high frequencies of multiple antigen specificities in the periphery and in the tumor. Prime-boost treatment reduced tumor-infiltrating regulatory CD4+ T cells whilst increasing cross-presenting dendritic cells in tumor-draining lymph nodes. In conclusion, heterologous prime-boost vaccination possesses the ability to induce a potent anti-tumor response in both immune-excluded and immune-infiltrated mouse tumor models. Additionally, this study highlights the design of a multi-epitope vaccine for cancer immunotherapy.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…with 10 7 TCID 50 VSV-GP. Vaccination schedules for the respective tumor models were performed as described [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Hofer

Rossi

Carboni

et al. 2021

Cancers

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A Biomimetic Autophagosomes‐Based Nanovaccine Boosts Anticancer Immunity

Qu,

Cui,

Sun

et al. 2024

Advanced Materials

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Personalized cancer vaccines based on tumor cell lysates offer promise for cancer immunotherapy yet fail to elicit a robust therapeutic effect due to the weak immunogenicity of tumor antigens. Autophagosomes, obtained from pleural effusions and ascites of cancer patients, have been identified as abundant reservoirs of tumor neoantigens that exhibit heightened immunogenicity. However, their potential as personalized cancer vaccines have been constrained by suboptimal lymphatic‐targeting performances and challenges in antigen‐presenting cell endocytosis. Here,a reinforced biomimetic autophagosome‐based (BAPs) nanovaccine generated by precisely amalgamating autophagosome‐derived neoantigens and two types of adjuvants capable of targeting lymph nodes is developed to potently elicit antitumor immunity. The redox‐responsive BAPs facilitate cytosolic vaccine opening within antigen‐presenting cells, thereby exposing adjuvants and antigens to stimulate a strong immune response. BAPs evoke broad‐spectrum T‐cell responses, culminating in the effective eradication of 71.4% of established tumors. Notably, BAPs vaccination triggers enduring T‐cell responses that confer robust protection, with 100% of mice shielded against tumor rechallenge and a significant reduction in tumor incidence by 87.5%. Furthermore, BAPs synergize with checkpoint blockade therapy to inhibit tumor growth in the poorly immunogenic breast cancer model. The biomimetic approach presents a powerful nanovaccine formula with high versatility for personalized cancer immunotherapy.

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Pseudocowpox virus, a novel vector to enhance the therapeutic efficacy of antitumor vaccination

et al. 2022

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Objective. Antitumor viral vaccines, and more particularly poxviral vaccines, represent an active field for clinical development and translational research. To improve the efficacy and treatment outcome, new viral vectors are sought, with emphasis on their abilities to stimulate innate immunity, to display tumor antigens and to induce a specific T-cell response. Methods. We screened for a new poxviral backbone with improved innate and adaptive immune stimulation using IFN-a secretion levels in infected PBMC cultures as selection criteria. Assessment of virus effectiveness was made in vitro and in vivo. Results. The bovine pseudocowpox virus (PCPV) stood out among several poxviruses for its ability to induce significant secretion of IFN-a. PCPV produced efficient activation of human monocytes and dendritic cells, degranulation of NK cells and reversed MDSC-induced T-cell suppression, without being offensive to activated T cells. A PCPV-based vaccine, encoding the HPV16 E7 protein (PCPV-E7), stimulated strong antigen-specific Tcell responses in TC1 tumor-bearing mice. Complete regression of tumors was obtained in a CD8 + T-cell-dependent manner after intratumoral injection of PCPV-E7, followed by intravenous injection of the cancer vaccine MVA-E7. PCPV also proved active when injected repeatedly intratumorally in MC38 tumor-bearing mice, generating tumor-specific T-cell responses without encoding a specific MC38 antigen. From a translational perspective, we demonstrated that PCPV-E7 effectively stimulated IFN-c production by T cells from tumor-draining lymph nodes of HPV + -infected cancer patients. Conclusion. We propose PCPV as a viral vector suitable for vaccination in the field of personalised cancer vaccines, in particular for heterologous prime-boost regimens.

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A modular self-adjuvanting cancer vaccine combined with an oncolytic vaccine induces potent antitumor immunity

Cited by 37 publications

References 50 publications

Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

Heterologous Prime-Boost Vaccination with a Peptide-Based Vaccine and Viral Vector Reshapes Dendritic Cell, CD4+ and CD8+ T Cell Phenotypes to Improve the Antitumor Therapeutic Effect

A Biomimetic Autophagosomes‐Based Nanovaccine Boosts Anticancer Immunity

Pseudocowpox virus, a novel vector to enhance the therapeutic efficacy of antitumor vaccination

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