Co-delivery of PSMA antigen epitope and mGM-CSF with a cholera toxin-like chimeric protein suppressed prostate tumor growth via activating dendritic cells and promoting CTL responses.

Lin, D ; He, H ; et al.

In: Vaccine, Jg. 39 (2021-03-12), Heft 11, S. 1609-1620

academicJournal

Subunit vaccines derived from tumor antigens play a role in tumor therapy because of their unique advantages. However, because of the weak immunogenicity of peptides in subunit vaccines, it is difficult to trigger an effective cytotoxic T lymphocyte (CTL) response, which is critical for cancer therapy. A requirement for the activation of CTL cells by exogenous antigens is the stimulation of antigen presenting cells (APC) with the help of adjuvants and cross-presentation to T lymphocytes. Standard nonconjugated adjuvant-peptide mixtures do not ensure co-targeting of the antigen and the adjuvant to the same APC, which limits the effects of adjuvants. In this study, a fusion protein consisting of murine granulocyte-macrophage colony stimulating factor (mGM-CSF) fused with CTA2 (A2 subunit of cholera toxin) was generated and assembled with CTB-PSMA624-632 (prostate specific membrane antigen (PSMA) peptide 624-632 fused to CTB) to obtain a cholera toxin-like protein. The chimeric protein retained the biological activity of mGM-CSF and had stronger GM1 binding activity than (CTB-PSMA624-632)5. C57BL/6J mice immunized with the CT-like chimeric protein exhibited delayed tumor growth following challenge with human PSMA-EGFP-expressing RM-1 cells. Experiment results showed that the CT-like chimeric protein could induce the maturation of DC cells and improve CTL responses. Overall, these results indicate that the nasal administration of a CT-like chimeric protein vaccine results in the development of effective immunity against prostate tumor cells and might be useful for future clinical anti-tumoral applications.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Titel:	Co-delivery of PSMA antigen epitope and mGM-CSF with a cholera toxin-like chimeric protein suppressed prostate tumor growth via activating dendritic cells and promoting CTL responses.
Autor/in / Beteiligte Person:	Lin, D ; He, H ; Sun, J ; He, X ; Long, W ; Cui, X ; Sun, Y ; Zhao, S ; Zheng, X ; Zeng, Z ; Zhang, K ; Wang, H
Zeitschrift:	Vaccine, Jg. 39 (2021-03-12), Heft 11, S. 1609-1620
Veröffentlichung:	Amsterdam, The Netherlands : Elsevier Science ; <i>Original Publication</i>: [Guildford, Surrey, UK] : Butterworths, [c1983-, 2021
Medientyp:	academicJournal
ISSN:	1873-2518 (electronic)
DOI:	10.1016/j.vaccine.2021.02.002
Schlagwort:	Animals Antigens, Surface Cholera Toxin Dendritic Cells Epitopes Glutamate Carboxypeptidase II Humans Macrophage Colony-Stimulating Factor Male Mice Mice, Inbred C57BL Recombinant Fusion Proteins genetics Prostatic Neoplasms therapy T-Lymphocytes, Cytotoxic
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Vaccine] 2021 Mar 12; Vol. 39 (11), pp. 1609-1620. <i>Date of Electronic Publication: </i>2021 Feb 19. MeSH Terms: Prostatic Neoplasms* / therapy ; T-Lymphocytes, Cytotoxic* ; Animals ; Antigens, Surface ; Cholera Toxin ; Dendritic Cells ; Epitopes ; Glutamate Carboxypeptidase II ; Humans ; Macrophage Colony-Stimulating Factor ; Male ; Mice ; Mice, Inbred C57BL ; Recombinant Fusion Proteins / genetics Contributed Indexing: Keywords: CTL responses; DC; Nasal administration; PSMA; Subunit vaccine; mGM-CSF Substance Nomenclature: 0 (Antigens, Surface) ; 0 (Epitopes) ; 0 (Recombinant Fusion Proteins) ; 81627-83-0 (Macrophage Colony-Stimulating Factor) ; 9012-63-9 (Cholera Toxin) ; EC 3.4.17.21 (FOLH1 protein, human) ; EC 3.4.17.21 (Glutamate Carboxypeptidase II) Entry Date(s): Date Created: 20210222 Date Completed: 20210524 Latest Revision: 20210524 Update Code: 20231215

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