Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cells and Mice
2.2. Patients
2.3. Preparation of GNP-LLO91–99 Nanovaccines
2.4. Isolation of MoDCs from Healthy Donors and Patients and Preparation of Murine DCs
2.5. Direct and Immunogenic Apoptosis of Melanoma and Bladder Tumor Cells
2.6. Bladder Tumor Auto Transplants Followed by GNP-LLO91–99 and ICI Immunotherapies
2.7. FACS Analysis and Cytokines
2.8. Statistical Analysis
3. Results and Discussion
3.1. GNP-LLO91–99 Nanovaccines Showed No Toxicity in Human MoDCs or Mice
3.2. GNP-LLO91–99 Nanovaccines Served as Adjuvants for Human MoDCs of Oncologic Patients
3.3. GNP-LLO91–99 Nanovaccines Induced Immunogenic Apoptosis in Bladder Tumors
3.4. Mechanisms of Anti-Neoplastic Abilities of GNP-LLO91–99 Nanovaccines in Mice Models of Melanoma and BC
3.5. GNP-LLO91–99 Nanovaccines Are Effective Immunotherapies That Blocked Immunosuppression
4. Conclusions
5. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient Code | Clinical Symptoms and Treatment a | IL-12 b,* | IL-6 | IL-10 | TNF-α |
---|---|---|---|---|---|
MEL-1 | Metastatic melanoma (IV) NT | 0.3 ± 0.1 | 6.4 ± 0.9 | 5.6± 0.9 | 6.25 ± 0.1 |
MEL-1 + GNP-LLO91–99 | Metastatic melanoma (IV) NT | 4.7 ± 0.1 | 2.22 ± 0.2 | 1.61 ± 0.1 | 66 ± 1.3 |
MEL-2 | Nodular melanoma (IIIB) surgery | 0.5 ± 0.1 | 6.1 ± 0.1 | 6.6 ± 0.1 | 8.78 ± 0.1 |
MEL-2 + GNP-LLO91–99 | Nodular melanoma (IIIB) surgery | 6.5 ± 0.2 | 2.07 ± 0.1 | 1.7 ± 0.1 | 50 ± 1.2 |
BC-1 | Lung–bladder carcinoma Cisplatin–etoposide | 0.2 ± 0.1 | 6.0 ± 0.1 | 4.6 ± 0.1 | 7.8 ± 0.1 |
BC-1 + GNP-LLO91–99 | Lung–bladder carcinoma Cisplatin–etoposide | 6.4 ± 0.1 | 2.3 ± 0.1 | 1.2 ± 0.1 | 220 ± 1.4 |
BC-2 | Urothelial bladder carcinoma NT | 0.3 ± 0.2 | 7.1 ± 0.2 | 5.1 ± 0.2 | 8.1 ± 0.1 |
BC-2 + GNP-LLO91–99 | Urothelial bladder carcinoma NT | 7.2 ± 0.3 | 2.1 ± 0.1 | 0.9 ± 0.2 | 204 ± 1.6 |
CONT | NONE | 0.8 ± 0.1 | 3.1 ± 0.1 | 2.4 ± 0.1 | 2.0 ± 0.1 |
CONT + GNP | NONE | 0.7 ± 0.1 | 2.8 ± 0.1 | 2.3 ± 0.1 | 1.8 ± 0.1 |
CONT + GNP-LLO91–99 | NONE | 6.0 ± 0.2 | 4.1 ± 0.2 | 3.5 ± 0.1 | 150 ± 0.2 |
Tumor Cell Line and Treatment a | Day 7 | Day 14 | Day 23 | ||||||
---|---|---|---|---|---|---|---|---|---|
SR c | U | TV d | SR | U | TV | SR | U | TV | |
MB49 + GNP-LLO91–99 b | 100% ± 1 | - | 426 ± 5 | 100% ± 1 | - | 436 ± 11 | 100% ± 1 | - | 490 ± 10 |
B16.F10 + GNP-LLO91–99 | 100% ± 1 | - | 460 ± 2 | 100% ± 2 | - | 470 ± 13 | 100% ± 2 | - | 490 ± 9 |
MB49-NT | 85% ± 2 | - | 1080 ± 5 | 45% ± 5 | +/− | 1680 ± 16 | 16% ± 2 | + | 4921 ± 19 |
B16.F10-NT | 84% ± 2 | - | 1090 ± 6 | 42% ± 2 | +/− | 1690 ± 19 | 10% ± 2 | + | 5322 ± 20 |
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Terán-Navarro, H.; Zeoli, A.; Salines-Cuevas, D.; Marradi, M.; Montoya, N.; Gonzalez-Lopez, E.; Ocejo-Vinyals, J.G.; Dominguez-Esteban, M.; Gutierrez-Baños, J.L.; Campos-Juanatey, F.; et al. Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors. Cancers 2022, 14, 2413. https://doi.org/10.3390/cancers14102413
Terán-Navarro H, Zeoli A, Salines-Cuevas D, Marradi M, Montoya N, Gonzalez-Lopez E, Ocejo-Vinyals JG, Dominguez-Esteban M, Gutierrez-Baños JL, Campos-Juanatey F, et al. Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors. Cancers. 2022; 14(10):2413. https://doi.org/10.3390/cancers14102413
Chicago/Turabian StyleTerán-Navarro, Hector, Andrea Zeoli, David Salines-Cuevas, Marco Marradi, Noemi Montoya, Elena Gonzalez-Lopez, Javier Gonzalo Ocejo-Vinyals, Mario Dominguez-Esteban, Jose Luis Gutierrez-Baños, Felix Campos-Juanatey, and et al. 2022. "Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors" Cancers 14, no. 10: 2413. https://doi.org/10.3390/cancers14102413
APA StyleTerán-Navarro, H., Zeoli, A., Salines-Cuevas, D., Marradi, M., Montoya, N., Gonzalez-Lopez, E., Ocejo-Vinyals, J. G., Dominguez-Esteban, M., Gutierrez-Baños, J. L., Campos-Juanatey, F., Yañez-Diaz, S., Garcia-Castaño, A., Rivera, F., Duran, I., & Alvarez-Dominguez, C. (2022). Gold Glyconanoparticles Combined with 91–99 Peptide of the Bacterial Toxin, Listeriolysin O, Are Efficient Immunotherapies in Experimental Bladder Tumors. Cancers, 14(10), 2413. https://doi.org/10.3390/cancers14102413