Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC)
Abstract
:1. Introduction
2. Materials and Methods
2.1. Peptide Selection, Design and Peptide Synthesis
2.2. Cell Lines and Inhibitors
2.3. Rabbits
2.4. MTT Cell Growth Proliferation Assay.
2.5. Receptor Phosphorylation Assay
2.6. Caspase Activity Assay for Apoptosis
2.7. Antibody Dependent Cellular Cytotoxicity (ADCC)
2.8. Western Blotting
2.9. Statistical Analysis
3. Results and Discussion
3.1. Epitope Selection, Design, Synthesis and Characterization
3.2. Single and Combination Treatment with Peptide Mimics or Peptide Vaccine Antibodies of HER-1 and HER-2 in EC or HER-1 and IGF-1R in TNBC Inhibits Proliferation of Cells in an MTT Assay
Peptides | Amino Acid Sequence of HER-1,HER-2 and IGF-1R Peptides | Mol.Wt (Da) |
---|---|---|
HER-1 (418–435) | Ac-SLNITSLGLRSLKEISDG-OH | 1944 |
HER-2 (266–296) | LHCPALVTYNTDTFESMPNPEGRYTFGASCV-OH | 3420 |
HER-2 (597–626) | VARCPSGVKPDLSYMPIWKFPDEEGACQPL-OH | 3333 |
IGF-1R (56–81) | Ac-LLFRVAGLESLGDLFPNLTVIRGWKL-NH2 | 2969 |
IGF-1R (233–251) | Ac-ACPPNTYRFEGWRCVDRDF-NH2 | 2372 |
MVF-HER-1 (418–435) | KLLSLIKGVIVHRLEGVE-GPSL-SLNITSLGLRSLKEISDG-OH | 4242 |
MVF-HER-2 (266–296) | KLLSLIKGVIVHRLEGVE-GPSL-LHCPALVTYNTDTFESMPNPEGRYTFGASCV-OH | 5757 |
MVF-HER-2 (597–626) | KLLSLIKGVIVHRLEGVE-GPSL-VARCPSGVKPDLSYMPIWKFPDEEGACQPL-OH | 5672 |
MVF-IGF-1R (56–81) | KLLSLIKGVIVHRLEGVE-LSPG-LLFRVAGLESLGDLFPNLTVIRGWKL-NH2 | 5267 |
MVF-IGF-1R (233–251) | Ac-KLLSLIKGVIVHRLEGVE-GPSL-Ac-ACPPNTYRFEGWRCVDRDF-NH2 | 4712 |
3.3. Peptide Vaccine Antibodies Induce ADCC of OE19 and TNBC Cells in Vitro
3.4. Single and Combination Treatment with Peptide Mimics or Peptide Vaccine Antibodies of HER-1 and HER-2 in EC or HER-1 and IGF-1R in TNBC down Regulates Receptor Phosphorylation in Vitro
3.5. Apoptosis Determination of OE19 and MDA-MB-231 Cancer Cells in Vitro by Caspase Activity Assay
4. Discussion
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Overholser, J.; Ambegaokar, K.H.; Eze, S.M.; Sanabria-Figueroa, E.; Nahta, R.; Bekaii-Saab, T.; Kaumaya, P.T.P. Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC). Vaccines 2015, 3, 519-543. https://doi.org/10.3390/vaccines3030519
Overholser J, Ambegaokar KH, Eze SM, Sanabria-Figueroa E, Nahta R, Bekaii-Saab T, Kaumaya PTP. Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC). Vaccines. 2015; 3(3):519-543. https://doi.org/10.3390/vaccines3030519
Chicago/Turabian StyleOverholser, Jay, Kristen Henkins Ambegaokar, Siobhan M. Eze, Eduardo Sanabria-Figueroa, Rita Nahta, Tanios Bekaii-Saab, and Pravin T.P. Kaumaya. 2015. "Anti-Tumor Effects of Peptide Therapeutic and Peptide Vaccine Antibody Co-targeting HER-1 and HER-2 in Esophageal Cancer (EC) and HER-1 and IGF-1R in Triple-Negative Breast Cancer (TNBC)" Vaccines 3, no. 3: 519-543. https://doi.org/10.3390/vaccines3030519