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Cited by 3Immunotherapy and Immune ResponsesT-cell and B-cell ImmunologyCancer Immunotherapy and Biomarkers

Co-Delivery of the Human NY-ESO-1 Tumor-Associated Antigen and Alpha-GalactosylCeramide by Filamentous Bacteriophages Strongly Enhances the Expansion of Tumor-Specific CD8+ T Cells

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Manco, Roberta, D’Apice, Luciana, Trovato, Maria, Lione, Lucia, Salvatori, Erika, Pinto, Eleonora, Compagnone, Mirco, Aurisicchio, Luigi +2 more·2023·Viruses
DOI 10.3390/v15030672PMC PMC10059692
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Abstract

Tumor-associated antigens (TAAs) represent attractive targets in the development of anti-cancer vaccines. The filamentous bacteriophage is a safe and versatile delivery nanosystem, and recombinant bacteriophages expressing TAA-derived peptides at a high density on the viral coat proteins improve TAA immunogenicity, triggering effective in vivo anti-tumor responses. To enhance the efficacy of the bacteriophage as an anti-tumor vaccine, we designed and generated phage particles expressing a CD8+ peptide derived from the human cancer germline antigen NY-ESO-1 decorated with the immunologically active lipid alpha-GalactosylCeramide (α-GalCer), a potent activator of invariant natural killer T (iNKT) cells. The immune response to phage expressing the human TAA NY-ESO-1 and delivering α-GalCer, namely fdNY-ESO-1/α-GalCer, was analyzed either in vitro or in vivo, using an HLA-A2 transgenic mouse model (HHK). By using NY-ESO-1-specific TCR-engineered T cells and iNKT hybridoma cells, we observed the efficacy of the fdNY-ESO-1/α-GalCer co-delivery strategy at inducing activation of both the cell subsets. Moreover, in vivo administration of fdNY-ESO-1 decorated with α-GalCer lipid in the absence of adjuvants strongly enhances the expansion of NY-ESO-1-specific CD8+ T cells in HHK mice. In conclusion, the filamentous bacteriophage delivering TAA-derived peptides and the α-GalCer lipid may represent a novel and promising anti-tumor vaccination strategy.

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  • M13 phages presenting NY-ESO-1 activated dendritic cells and primed CD8+ T cells, resulting in enhanced antitumor activity.

    “Similarly, M13 phages presenting the cancer-testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) activated dendritic cells and primed CD8+ T cells, resulting in enhanced antitumor activity [82,83]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [83]

    The Results (§§3.2–3.4; page numbers unavailable) report dendritic-cell maturation, activation of NY-ESO-1-specific T cells, and increased antigen-specific CD8+ T cells in immunized mice, particularly with phages co-delivering α-GalCer. They do not show that this produced enhanced antitumor activity: the study measured immune responses, not tumor outcomes. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • Together, these studies identify well-defined candidates for first-in-human evaluation.

    “Together, these studies identify well-defined candidates for first-in-human evaluation while underscoring the need to address translational barriers related to scalability, regulatory approval, and patient stratification.”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [83]

    The Discussion describes the fdNY-ESO-1/α-GalCer phage as a potential vaccine model against human cancer, supporting its identification as a candidate. But it explicitly calls for further studies of immune responses in humans and does not identify it as ready for first-in-human evaluation. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Engineered phage vaccines displaying tumor-associated antigens or delivering immunostimulatory cargo have demonstrated robust antitumor immunity and survival benefits in multiple mouse models.

    “In parallel, engineered phage vaccines displaying tumor-associated antigens or delivering immunostimulatory cargo have demonstrated robust antitumor immunity and survival benefits in multiple mouse models [80–85]”

    From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [83]

    The Introduction reports that an earlier phage vaccine delayed tumor growth in animal models, and the Discussion reports strong expansion of tumor-specific CD8+ T cells in this paper’s HHK mice. This paper does not report a survival benefit, and its own in vivo experiment assessed immune response rather than tumor outcomes across multiple mouse models. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Manco, R., D’Apice, L., Trovato, M., Lione, L., Salvatori, E., Pinto, E., Compagnone, M., Aurisicchio, L., De Berardinis, P., & Sartorius, R.
Affiliations
  • National Research Council (IT)
  • Takis Biotech, 00128 Rome, Italy
  • Neomatrix Biotech (Italy) (IT)
  • Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), 80131 Naples, Italy
Corresponding author
Sartorius, Rossella
ORCID
Venue
Viruses
Publisher
MDPI AG
Published
2023-03-02
Volume
15
Issue
3
Pages
672
ISSN
1999-4915 (ISSN-L)
DOI
10.3390/v15030672
PMC
PMC10059692
OpenAlex
W4323043819
Cited by
3
References
1
Citations by year
2026: 2 · 2023: 1
FWCI
0.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Viruses (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • FESR PON “Ricerca e Innovazione” (PON ARS01_00906, CCI 2014IT16M2OP005)
  • Dottorati Innovativi con caratterizzazione Industriale (PON ARS01_00906, CCI 2014IT16M2OP005)
  • “Luigi Vanvitelli” Campania University (PON ARS01_00906, CCI 2014IT16M2OP005)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
NY-ESO-1, alpha-galactosylceramide, filamentous bacteriophage, cancer vaccines, tumor-associated antigens, CD8+ T cells, invariant natural killer T cells, cancer germline antigens, phage display, lipid adjuvants, HLA-A2 transgenic mice, T cell expansion
MeSH terms
Animals, Antibodies, Antigens, Neoplasm, Galactosylceramides, Humans, Membrane Proteins, Mice, Transgenic, Neoplasms, Peptides, CD8-Positive T-Lymphocytes, Mice

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