HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model
Breast cancer is the most common invasive cancer diagnosed among women. A cancer vaccine has been recognized as a form of immunotherapy with a prominent position in the prevention and treatment of breast cancer. The majority of current breast cancer vaccination strategies aim to stimulate antitumor...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Multidisciplinary Digital Publishing Institute
2021
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| Online Access: | http://psasir.upm.edu.my/id/eprint/97517/1/ABSTRACT.pdf |
| _version_ | 1796983408743677952 |
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| author | Nordin, Muhammad Luqman Mohamad Norpi, Abdin Shakirin Pei, Yuen Ng Yusoff, Khatijah Abu, Nadiah Kue, Peng Lim Azmi, Fazren |
| author_facet | Nordin, Muhammad Luqman Mohamad Norpi, Abdin Shakirin Pei, Yuen Ng Yusoff, Khatijah Abu, Nadiah Kue, Peng Lim Azmi, Fazren |
| author_sort | Nordin, Muhammad Luqman |
| collection | UPM |
| description | Breast cancer is the most common invasive cancer diagnosed among women. A cancer vaccine has been recognized as a form of immunotherapy with a prominent position in the prevention and treatment of breast cancer. The majority of current breast cancer vaccination strategies aim to stimulate antitumor T-cell responses of the HER2/neu oncogene, which is abnormally expressed in breast cancer cells. However, the role of the B-cell humoral response is often underappreciated in the cancer vaccine design. We have advanced this idea by elucidating the role of B-cells in cancer vaccination by designing a chimeric antigenic peptide possessing both cytotoxic T lymphocytes (GP2) and B-cell (P4) peptide epitopes derived from HER2/neu. The chimeric peptide (GP2–P4) was further conjugated to a carrier protein (KLH), forming a KLH–GP2–P4 conjugate. The immunogenicity of KLH–GP2–P4 was compared with KLH–GP2 (lacking the B-cell epitope) in BALB/c mice. Mice immunized with KLH–GP2–P4 elicited more potent antigen-specific neutralizing antibodies against syngeneic TUBO cells (cancer cell line overexpressing HER2/neu) that was governed by a balanced Th1/Th2 polarization in comparison to KLH–GP2. Subsequently, these immune responses led to greater inhibition of tumor growth and longer survival in TUBO tumor-bearing mice in both prophylactic and therapeutic challenge experiments. Overall, our data demonstrated that the B-cell epitope has a profound effect in orchestrating an efficacious antitumor immunity. Thus, a multi-epitope peptide vaccine encompassing cytotoxic T-lymphocytes, T-helper and B-cell epitopes represents a promising strategy in developing cancer vaccines with a preventive and therapeutic modality for the effective management of breast cancer. |
| first_indexed | 2024-03-06T11:06:08Z |
| format | Article |
| id | upm.eprints-97517 |
| institution | Universiti Putra Malaysia |
| language | English |
| last_indexed | 2024-03-06T11:06:08Z |
| publishDate | 2021 |
| publisher | Multidisciplinary Digital Publishing Institute |
| record_format | dspace |
| spelling | upm.eprints-975172022-07-27T06:17:47Z http://psasir.upm.edu.my/id/eprint/97517/ HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model Nordin, Muhammad Luqman Mohamad Norpi, Abdin Shakirin Pei, Yuen Ng Yusoff, Khatijah Abu, Nadiah Kue, Peng Lim Azmi, Fazren Breast cancer is the most common invasive cancer diagnosed among women. A cancer vaccine has been recognized as a form of immunotherapy with a prominent position in the prevention and treatment of breast cancer. The majority of current breast cancer vaccination strategies aim to stimulate antitumor T-cell responses of the HER2/neu oncogene, which is abnormally expressed in breast cancer cells. However, the role of the B-cell humoral response is often underappreciated in the cancer vaccine design. We have advanced this idea by elucidating the role of B-cells in cancer vaccination by designing a chimeric antigenic peptide possessing both cytotoxic T lymphocytes (GP2) and B-cell (P4) peptide epitopes derived from HER2/neu. The chimeric peptide (GP2–P4) was further conjugated to a carrier protein (KLH), forming a KLH–GP2–P4 conjugate. The immunogenicity of KLH–GP2–P4 was compared with KLH–GP2 (lacking the B-cell epitope) in BALB/c mice. Mice immunized with KLH–GP2–P4 elicited more potent antigen-specific neutralizing antibodies against syngeneic TUBO cells (cancer cell line overexpressing HER2/neu) that was governed by a balanced Th1/Th2 polarization in comparison to KLH–GP2. Subsequently, these immune responses led to greater inhibition of tumor growth and longer survival in TUBO tumor-bearing mice in both prophylactic and therapeutic challenge experiments. Overall, our data demonstrated that the B-cell epitope has a profound effect in orchestrating an efficacious antitumor immunity. Thus, a multi-epitope peptide vaccine encompassing cytotoxic T-lymphocytes, T-helper and B-cell epitopes represents a promising strategy in developing cancer vaccines with a preventive and therapeutic modality for the effective management of breast cancer. Multidisciplinary Digital Publishing Institute 2021 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/97517/1/ABSTRACT.pdf Nordin, Muhammad Luqman and Mohamad Norpi, Abdin Shakirin and Pei, Yuen Ng and Yusoff, Khatijah and Abu, Nadiah and Kue, Peng Lim and Azmi, Fazren (2021) HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model. Cancers, 13 (19). pp. 1-16. ISSN 2072-6694 https://www.mdpi.com/2072-6694/13/19/4958 10.3390/cancers13194958 |
| spellingShingle | Nordin, Muhammad Luqman Mohamad Norpi, Abdin Shakirin Pei, Yuen Ng Yusoff, Khatijah Abu, Nadiah Kue, Peng Lim Azmi, Fazren HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model |
| title | HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model |
| title_full | HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model |
| title_fullStr | HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model |
| title_full_unstemmed | HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model |
| title_short | HER2/neu-based peptide vaccination-pulsed with B-cell epitope induced efficient prophylactic and therapeutic antitumor activities in TUBO breast cancer mice model |
| title_sort | her2 neu based peptide vaccination pulsed with b cell epitope induced efficient prophylactic and therapeutic antitumor activities in tubo breast cancer mice model |
| url | http://psasir.upm.edu.my/id/eprint/97517/1/ABSTRACT.pdf |
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