Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma
Abstract
:1. Introduction
2. Experimental Section
2.1. Mouse Strains
2.2. Tumor Model (B16-OVA, B16 Melanoma)
2.3. Vaccine Preparation and Route of Immunization
2.4. Checkpoint Inhibitor Combination Therapy
2.5. Cellular Processing and Detection of OVA-Specific CD8+ T Cells
2.6. Statistical Analysis
2.7. Processing and Immunohistochemical Detection of Tumor-Infiltrating Immune Cells
2.8. Histological Scoring
3. Results
3.1. SLA–OVA (adm) Immunization Synergizes with Anti-CTLA-4 and Anti-PD-1 Therapy to Provide Protection in a B16-OVA Melanoma Model
3.2. SLA–OVA (adm) Therapy Increased the Frequencies of OVA-CD8+ T Cells in the Spleen and Tumor
3.3. Histological Properties of B16 Tumors
3.4. Immunohistochemical Evaluation of CD8+ T Cells in B16-OVA Tumor-Bearing Mice Receiving SLA–OVA and Checkpoint Therapy
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Frequency of OVA-CD8+ T Cells of All CD8+ T Cells in the Spleen and Tumor at the Humane Endpoint | ||||
---|---|---|---|---|
Spleen | Tumour | |||
Geometric Mean | %95 CI (Lower + Upper) | Geometric Mean | %95 CI (Lower + Upper) | |
SLA-OVA (adm) | 1.13 | 0.38 and 1.79 | 0.55 | 0.23 and 1.35 |
Anti- CTLA4 + anti-PD-1 | 0.17 | −0.03 and 0.56 | 0.56 | 0.17 and 3.12 |
SLA-OVA (adm) + anti-CTLA4 + anti-PD-1 | 0.27 | 0.14 and 1.38 | 1.85 | 0.18 and 5.50 |
SLA-OVA (enc) + anti-CTLA4 + anti-PD-1 | 1.49 | 0.44 and 3.07 | 8.02 | 0.41 and 21.97 |
MS-OVA (enc) + anti-CTLA4 + anti-PD-1 | 1.27 | 0.55 and 1.37 | 1.74 | 0.67 and 3.04 |
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Stark, F.C.; Agbayani, G.; Sandhu, J.K.; Akache, B.; McPherson, C.; Deschatelets, L.; Dudani, R.; Hewitt, M.; Jia, Y.; Krishnan, L.; et al. Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma. Biomedicines 2019, 7, 91. https://doi.org/10.3390/biomedicines7040091
Stark FC, Agbayani G, Sandhu JK, Akache B, McPherson C, Deschatelets L, Dudani R, Hewitt M, Jia Y, Krishnan L, et al. Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma. Biomedicines. 2019; 7(4):91. https://doi.org/10.3390/biomedicines7040091
Chicago/Turabian StyleStark, Felicity C., Gerard Agbayani, Jagdeep K. Sandhu, Bassel Akache, Charis McPherson, Lise Deschatelets, Renu Dudani, Melissa Hewitt, Yimei Jia, Lakshmi Krishnan, and et al. 2019. "Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma" Biomedicines 7, no. 4: 91. https://doi.org/10.3390/biomedicines7040091