Firdaus Farrhana Z, Bartlett Stacey, Hussein Waleed M, Lu Lantian, Wright Quentin, Huang Wenbin, Nahar Ummey J, Yang Jieru, Khongkow Mattaka, Veitch Margaret, Koirala Prashamsa, Ruktanonchai Uracha R, Monteiro Michael J, Gonzalez Cruz Jazmina L, Stephenson Rachel J, Wells James W, Toth Istvan, Skwarczynski Mariusz
School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Faculty of Medicine, Frazer Institute, The University of Queensland, Brisbane, QLD 4102, Australia.
Pharmaceutics. 2023 Feb 10;15(2):602. doi: 10.3390/pharmaceutics15020602.
Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant.
人乳头瘤病毒(HPV)是所有宫颈癌病例的致病原因。虽然有预防性疫苗,但基于肽的疫苗作为一种治疗策略仍在研究中。与传统的化疗和手术治疗策略相比,接种HPV疫苗是一种有前景的治疗选择,副作用较少。一种源自HPV-16 E7蛋白的名为8Qm的肽与佐剂联合使用,显示出作为治疗性疫苗的潜力。在此,首次研究了聚合天然氨基酸作为治疗性疫苗的自佐剂递送系统的能力。因此,通过标准固相肽合成将8Qm与聚亮氨酸偶联,并自组装成纳米颗粒或包封在脂质体中。携带8Qm偶联物的脂质体在单次免疫后显著提高了小鼠的存活率并减少了肿瘤生长。此外,这些脂质体消除了小鼠体内7天大的已形成的肿瘤。引入树突状细胞(DC)靶向部分以进一步提高疫苗效力,并在携带11天大肿瘤的小鼠中测试了新设计的脂质体疫苗。有趣的是,这些DC靶向部分并没有显著提高疫苗效力,而8Qm-聚亮氨酸偶联物的简单脂质体制剂在根除肿瘤方面仍然有效。总之,开发了一种基于肽的抗癌疫苗,该疫苗在没有经典佐剂帮助的情况下刺激了强烈的细胞免疫反应。