Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor Effects
Abstract
:1. Introduction
2. Results
2.1. Chemical Synthesis of the Vaccine Candidates
2.2. In Vitro Immunostimulatory Responses of the Vaccine Candidates
2.3. SZU251 + MUC1 + Al Inhibited 4T1 Mouse Breast Tumor Growth in the Prophylactic Schedule
2.4. SZU251 + MUC1 + Al Induced Tumor-Specific Immune Responses in the Prophylactic Schedule
2.5. SZU251 + MUC1 + Al Inhibited 4T1 Mouse Breast Tumor Growth in the Therapeutic Schedule
2.6. SZU251 + MUC1 + Al Induced Tumor-Specific Immune Responses in the Therapeutic Schedule
3. Discussion
4. Materials and Methods
4.1. Compounds
4.2. Mice and Cell Lines
4.3. HEK-Blue Assay
4.4. BMDCs Preparation
4.5. BMDCs Maturation
4.6. Spleen Lymphocytes Preparation
4.7. Analysis of Cytokine Levels by ELISA
4.8. Immunization of Mice
4.9. Analysis of Antibody Titers and Subtypes by ELISA
4.10. Analysis of Antigen Recognition Ability
4.11. Evaluation of Antitumor Effects in Vaccinated Mice
4.12. Detection of T Lymphocytes
4.13. Immunohistochemistry (IHC) Staining
4.14. Toxicity Studies
4.15. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Group | NaCl | Al | SZU251 + Al | MUC1 + Al | SZU251 + MUC1 + Al |
---|---|---|---|---|---|
WBC (109/L) | 30.05 ± 4.96 | 28.70 ± 9.49 | 27.68 ± 7.59 | 18.63 ± 5.74 | 13.85 ± 3.24 |
RBC (1012/L) | 11.17 ± 0.56 | 11.64 ± 0.95 | 11.74 ± 0.69 | 11.07 ± 0.71 | 11.40 ± 0.49 |
HGB (g/L) | 175.20 ± 7.73 | 186.50 ± 9.33 | 181.25 ± 5.56 | 171.20 ± 10.69 | 169.00 ± 8.69 |
HCT (%) | 55.40 ± 2.42 | 57.45 ± 4.62 | 55.24 ± 3.23 | 55.36 ± 3.23 | 54.12 ± 2.91 |
MCV (fL) | 49.66 ± 0.47 | 49.40 ± 0.86 | 47.11 ± 0.98 | 50.08 ± 1.00 | 47.52 ± 1.08 |
PLT (109/L) | 1022.67 ± 168.50 | 1045.50 ± 258.30 | 957.50 ± 208.63 | 795.50 ± 138.85 | 809.00 ± 43.70 |
Antibody | Titer | |||||
---|---|---|---|---|---|---|
NaCl | Al | SZU251 + Al | MUC1 + Al | SZU251 + MUC1 + Al | ||
IgG | Day 10 | 0 | 0 | 0 | 1000 | 16,000 |
Day 24 | 0 | 0 | 0 | 32,000 | 1,024,000 | |
Day 38 | 0 | 0 | 0 | 256,000 | 2,048,000 | |
IgG1 | Day 10 | 0 | 0 | 0 | 0 | 0 |
Day 24 | 0 | 0 | 0 | 8000 | 64,000 | |
Day 38 | 0 | 0 | 0 | 8000 | 128,000 | |
IgG2a | Day 10 | 0 | 0 | 0 | 0 | 32,000 |
Day 24 | 0 | 0 | 0 | 16,000 | 2,048,000 | |
Day 38 | 0 | 0 | 0 | 16,000 | 2,048,000 | |
IgM | Day 10 | 0 | 0 | 0 | 0 | 16,000 |
Day 24 | 0 | 0 | 0 | 4000 | 128,000 | |
Day 38 | 0 | 0 | 0 | 16,000 | 128,000 |
Group | NaCl | Al | SZU251 + Al | MUC1 + Al | SZU251 + MUC1 + Al |
---|---|---|---|---|---|
WBC (109/L) | 13.33 ± 0.78 | 9.68 ± 5.12 | 15.48 ± 5.31 | 12.60 ± 2.52 | 15.30 ± 3.48 |
RBC (1012/L) | 9.85 ± 0.40 | 10.00 ± 0.94 | 9.57 ± 0.33 | 8.70 ± 0.46 | 9.34 ± 0.81 |
HGB (g/L) | 144.80 ± 4.15 | 142.00 ± 7.00 | 144.40 ± 7.54 | 134.00 ± 5.29 | 140.20 ± 9.40 |
HCT (%) | 44.83 ± 1.35 | 45.93 ± 3.95 | 43.86 ± 1.95 | 40.56 ± 1.70 | 43.34 ± 3.67 |
MCV (fL) | 46.92 ± 0.47 | 46.03 ± 0.76 | 45.77 ± 0.21 | 46.98 ± 0.89 | 45.87 ± 0.35 |
PLT (109/L) | 739.40 ± 128.80 | 633.80 ± 288.80 | 1056.00 ± 214.99 | 933.40 ± 188.03 | 956.75 ± 231.80 |
Antibody | Titer | |||||
---|---|---|---|---|---|---|
NaCl | Al | SZU251 + Al | MUC1 + Al | SZU251 + MUC1 + Al | ||
IgG | Day 10 | 0 | 0 | 0 | 32,000 | 64,000 |
Day 20 | 0 | 0 | 0 | 128,000 | 1,024,000 | |
IgG1 | Day 10 | 0 | 0 | 0 | 0 | 0 |
Day 20 | 0 | 0 | 0 | 32,000 | 32,000 | |
IgG2a | Day 10 | 0 | 0 | 0 | 32,000 | 64,000 |
Day 20 | 0 | 0 | 0 | 32,000 | 1,024,000 | |
IgM | Day 10 | 0 | 0 | 0 | 8000 | 128,000 |
Day 20 | 0 | 0 | 0 | 32,000 | 256,000 |
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Zhang, S.; Liu, Y.; Zhou, J.; Wang, J.; Jin, G.; Wang, X. Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor Effects. Int. J. Mol. Sci. 2022, 23, 15130. https://doi.org/10.3390/ijms232315130
Zhang S, Liu Y, Zhou J, Wang J, Jin G, Wang X. Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor Effects. International Journal of Molecular Sciences. 2022; 23(23):15130. https://doi.org/10.3390/ijms232315130
Chicago/Turabian StyleZhang, Shuquan, Yu Liu, Ji Zhou, Jiaxin Wang, Guangyi Jin, and Xiaodong Wang. 2022. "Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor Effects" International Journal of Molecular Sciences 23, no. 23: 15130. https://doi.org/10.3390/ijms232315130
APA StyleZhang, S., Liu, Y., Zhou, J., Wang, J., Jin, G., & Wang, X. (2022). Breast Cancer Vaccine Containing a Novel Toll-like Receptor 7 Agonist and an Aluminum Adjuvant Exerts Antitumor Effects. International Journal of Molecular Sciences, 23(23), 15130. https://doi.org/10.3390/ijms232315130