Zare Hamed, Bakherad Hamid, Esfahani Arman Nasr, Aghamollaei Hossein, Gargari Seyed Latif Mousavi, Aliomrani Mahdi, Ebrahimizadeh Walead
Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Res Pharm Sci. 2024 Feb 6;19(1):73-82. doi: 10.4103/1735-5362.394822. eCollection 2024 Feb.
Treatment of malignancies with chemotherapy and surgery is often associated with disease recurrence and metastasis. Immunotherapy improves cancer treatment by creating an active response against tumor antigens. Various cancer cells express a large amount of glucose-regulated protein 78 (GRP78) protein on their surface. Stimulating the immune system against this antigen can expose cancer cells to the immune system. Herein, we investigated the effectiveness of a cGRP78-based vaccine against different cancer cells.
BALB/c mice were immunized with the cGRP78. The humoral immune response against different cancer cells was assessed by Cell-ELISA. The cellular immunity response was determined by splenocyte proliferation assay with different cancer antigens. The effect of vaccination on metastasis was investigated in vaccinated mice by injecting melanoma cancer cells into the tail of mice.
FINDINGS/RESULTS: These results indicated that the cGRP78 has acceptable antigenicity and stimulates the immune system to produce antibodies. After three injections, the amount of produced antibody was significantly different from the control group. Compared to the other three cell types, Hela and HepG2 showed the highest reaction to the serum of vaccinated mice. Cellular immunity against the B16F10 cell line had the best results compared to other cells. The metastasis results showed that after 30 days, the growth of B16F10 melanoma cancer cells was not noticeable in the lung tissue of vaccinated mice.
Considering the resistance of vaccinated mice to metastasis, this vaccine offers a promising prospect for cancer treatment by inhibiting the spread of cancer cells.
化疗和手术治疗恶性肿瘤常常伴随着疾病复发和转移。免疫疗法通过激发针对肿瘤抗原的主动反应来改善癌症治疗。各种癌细胞在其表面大量表达葡萄糖调节蛋白78(GRP78)。刺激免疫系统针对这种抗原可使癌细胞暴露于免疫系统。在此,我们研究了基于cGRP78的疫苗对不同癌细胞的有效性。
用cGRP78对BALB/c小鼠进行免疫。通过细胞酶联免疫吸附测定评估针对不同癌细胞的体液免疫反应。通过用不同癌症抗原进行脾细胞增殖测定来确定细胞免疫反应。通过将黑色素瘤癌细胞注射到小鼠尾部,在接种疫苗的小鼠中研究疫苗接种对转移的影响。
这些结果表明cGRP78具有可接受的抗原性,并刺激免疫系统产生抗体。三次注射后,产生的抗体量与对照组有显著差异。与其他三种细胞类型相比,Hela和HepG2对接种疫苗小鼠的血清反应最高。与其他细胞相比,针对B16F10细胞系的细胞免疫效果最佳。转移结果表明,30天后,接种疫苗小鼠肺组织中B16F10黑色素瘤癌细胞的生长不明显。
考虑到接种疫苗小鼠对转移的抵抗力,这种疫苗通过抑制癌细胞扩散为癌症治疗提供了一个有前景的前景。