Antitumor effect and mechanism of FZD7 polypeptide vaccine
The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cel...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.925495/full |
| _version_ | 1797997353214410752 |
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| author | Zhongke Hua Yu Han Kan Liu Hua Yang Cai Zhou Fengyi Chen Shenglan Nie Mengqing Li Qinyao Yu Yunpeng Wei Christina C. N. Wu Xiaomei Wang |
| author_facet | Zhongke Hua Yu Han Kan Liu Hua Yang Cai Zhou Fengyi Chen Shenglan Nie Mengqing Li Qinyao Yu Yunpeng Wei Christina C. N. Wu Xiaomei Wang |
| author_sort | Zhongke Hua |
| collection | DOAJ |
| description | The resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). In vivo and vitro tests were used to assess tumor cell inhibition. In vitro, the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response in vivo and in vitro, and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC. |
| first_indexed | 2024-04-11T10:31:32Z |
| format | Article |
| id | doaj.art-9d27984b7b3e4d9b915889d96c0b50eb |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T10:31:32Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-9d27984b7b3e4d9b915889d96c0b50eb2022-12-22T04:29:25ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-10-011210.3389/fonc.2022.925495925495Antitumor effect and mechanism of FZD7 polypeptide vaccineZhongke Hua0Yu Han1Kan Liu2Hua Yang3Cai Zhou4Fengyi Chen5Shenglan Nie6Mengqing Li7Qinyao Yu8Yunpeng Wei9Christina C. N. Wu10Xiaomei Wang11International Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaMoores Cancer Center, University of California, San Diego, La Jolla, CA, United StatesInternational Cancer Center, Shenzhen Key Lab of Synthetic Biology, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, ChinaThe resistant cells that proliferate after radiotherapy and chemotherapy are primarily tumor stem cells with high stem marker expression, and their presence is the primary cause of tumor dispersion. The Wnt signaling receptor Frizzled family receptor 7 (FZD7) is linked to the maintenance of stem cell features as well as cancer progression. Frizzled-7 (FZD7), a key receptor for Wnt/-catenin signaling, is overexpressed in TNBC, suggesting that it could be a viable target for cancer therapy. We employed bioinformatics to find the best-scoring peptide, chemically synthesized FZD7 epitope antigen, and binding toll-like receptor 7 agonists (T7). Under GMP conditions, peptides for vaccines were produced and purified (>95%). In vivo and vitro tests were used to assess tumor cell inhibition. In vitro, the FZD7-T7 vaccination can boost the maturity of BMDC cells considerably. In mice, the FZD7 - T7 vaccine elicited the greatest immunological response. Significant tumor development inhibition was seen in BALB/c mice treated with FZD7 - T7 in prevention experiments (P < 0.01). Multiple cytokines that promote cellular immune responses, such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), and IL-2 (P < 0.01), were shown to be considerably elevated in mice inoculated with FZD7- T7. Furthermore, we evaluated safety concerns in terms of vaccine composition to aid in the creation of successful next-generation vaccines. In conclusion, the FZD7-T7 vaccine can activate the immune response in vivo and in vitro, and play a role in tumor suppression. Our findings reveal a unique tumor-suppressive role for the FZD7 peptide in TNBC.https://www.frontiersin.org/articles/10.3389/fonc.2022.925495/fullcancer preventioncancer immunologyFZD7TLR7 agonistbreast cancer |
| spellingShingle | Zhongke Hua Yu Han Kan Liu Hua Yang Cai Zhou Fengyi Chen Shenglan Nie Mengqing Li Qinyao Yu Yunpeng Wei Christina C. N. Wu Xiaomei Wang Antitumor effect and mechanism of FZD7 polypeptide vaccine Frontiers in Oncology cancer prevention cancer immunology FZD7 TLR7 agonist breast cancer |
| title | Antitumor effect and mechanism of FZD7 polypeptide vaccine |
| title_full | Antitumor effect and mechanism of FZD7 polypeptide vaccine |
| title_fullStr | Antitumor effect and mechanism of FZD7 polypeptide vaccine |
| title_full_unstemmed | Antitumor effect and mechanism of FZD7 polypeptide vaccine |
| title_short | Antitumor effect and mechanism of FZD7 polypeptide vaccine |
| title_sort | antitumor effect and mechanism of fzd7 polypeptide vaccine |
| topic | cancer prevention cancer immunology FZD7 TLR7 agonist breast cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.925495/full |
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