دورية أكاديمية
The predominant Quillaja Saponaria fraction, QS-18, is safe and effective when formulated in a liposomal murine cancer peptide vaccine.
| العنوان: | The predominant Quillaja Saponaria fraction, QS-18, is safe and effective when formulated in a liposomal murine cancer peptide vaccine. |
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| المؤلفون: | Zhou S; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Song Y; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Nilam A; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Luo Y; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Huang WC; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA., Long MD; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Lovell JF; Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA. Electronic address: jflovell@buffalo.edu. |
| المصدر: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 May; Vol. 369, pp. 687-695. Date of Electronic Publication: 2024 Apr 12. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
| مواضيع طبية MeSH: | Liposomes* , Cancer Vaccines*/administration & dosage , Cancer Vaccines*/immunology , Quillaja*/chemistry , Adjuvants, Immunologic*/administration & dosage, Animals ; Female ; Mice, Inbred C57BL ; Vaccines, Subunit/administration & dosage ; Vaccines, Subunit/immunology ; Mice ; Quillaja Saponins ; Cytokines ; Saponins/administration & dosage ; Saponins/pharmacology ; Cell Line, Tumor ; Protein Subunit Vaccines |
| مستخلص: | Extracts of the Chilean soapbark tree, Quillaja Saponaria (QS) are the source of potent immune-stimulatory saponin compounds. This study compared the adjuvanticity and toxicity of QS-18 and QS-21, assessing the potential to substitute QS-18 in place of QS-21 for vaccine development. QS-18, the most abundant QS saponin fraction, has been largely overlooked due to safety concerns. We found that QS-18 spontaneously inserted into liposomes, thereby neutralizing hemolytic activity, and following administration did not induce local reactogenicity in a footpad swelling test in mice. With high-dose intramuscular administration, transient weight loss was minor, and QS-18 did not induce significantly more weight loss compared to a liposome vaccine adjuvant system lacking it. Two days after administration, no elevation of inflammatory cytokines was detected in murine serum. In a formulation including cobalt-porphyrin-phospholipid (CoPoP) for short peptide sequestration, QS-18 did not impact the formation of peptide nanoparticles. With immunization, QS-18 peptide particles induced higher levels of cancer neoepitope-specific and tumor-associated antigen-specific CD8 + T cells compared to QS-21 particles, without indication of greater toxicity based on mouse body weight. T cell receptor sequencing of antigen-specific CD8 + T cells showed that QS-18 induced significantly more T cell transcripts. In two murine cancer models, vaccination with QS-18 peptide particles induced a similar therapeutic effect as QS-21 particles, without indication of increased toxicity. Antigen-specific CD8 + T cells in the tumor microenvironment were found to express the exhaustion marker PD-1, pointing to the rationale for exploring combination therapy. Taken together, these data demonstrate that QS-18, when formulated in liposomes, can be a safe and effective adjuvant to induce tumor-inhibiting cellular responses in murine models with potential to facilitate or diminish costs of production for vaccine adjuvant systems. Further studies are warranted to assess liposomal QS-18 immunogic, reactogenic and toxicological profiles in mice and other animal species. Competing Interests: Declaration of competing interest J.F.L. and W.-C.H. hold interest in POP Biotechnologies. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Adjuvants; Liposomes; Peptides; Saponin; Vaccines |
| المشرفين على المادة: | 0 (Liposomes) 0 (Cancer Vaccines) 0 (Adjuvants, Immunologic) 0 (Vaccines, Subunit) 0 (Quillaja Saponins) 0 (Cytokines) 0 (Saponins) 0 (Protein Subunit Vaccines) |
| تواريخ الأحداث: | Date Created: 20240404 Date Completed: 20240522 Latest Revision: 20240523 |
| رمز التحديث: | 20240524 |
| DOI: | 10.1016/j.jconrel.2024.04.002 |
| PMID: | 38575073 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-4995 |
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| DOI: | 10.1016/j.jconrel.2024.04.002 |