Hamed Zare
1 
, Hamid Bakherad
2,3* , Arman Nasr Esfahani
2, Mohamad Norouzi
2, Hossein Aghamollaei
4, Seyed Latif Mousavi Gargari
5, Fatemeh Mahmoodi
6, Mahdi Aliomrani
7, Walead Ebrahimizadeh
81 Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran
2 Department of Pharmaceutical Biotechnology, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
3 Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
4 Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
5 Department of Biology, Faculty of Basic Science, Shahed University, Tehran, I.R. Iran
6 Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran
7 Department of Pharmacology and Toxicology, Isfahan Pharmaceutical Science Research Center, Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
8 Department of Surgery, Division of Urology, McGill University, and the Research Institute of the McGill University Health Centre (RI MUHC), Montreal, Quebec, Canada
Abstract
Introduction: Breast cancer is one of the most prevalent malignancies in women. Several treatment options are available today, including surgery, chemotherapy, and radiotherapy. Immunotherapy, as a highly specific therapy, involves adaptive immune responses and immunological memory. In our present research, we used the recombinant C-terminal domain of the GRP78 (glucose- regulated protein 78) protein to induce an immune response and investigate its therapeutic impact in the 4T1 breast cancer model.
Methods: BALB/c mice were immunized with the cGRP78 protein. The humoral immune response was assessed by ELISA. Then, BALB/c mice were injected subcutaneously with 1×106 4T1 tumor cells. Subsequently, tumor size and survival rate measurements, MTT, and cytokine assays were performed.
Results: The animals receiving the cGRP78 vaccine showed significantly more favorable survival and slower tumor growth rates compared with unvaccinated tumor-bearing mice as the negative control mice. Circulating levels of tumoricidal cytokines such as IFNγ were higher, whereas tolerogenic cytokines such as IL-2, 6, and 10 either did not increase or had a decreasing trend in mice receiving cGRP78.
Conclusion: cGRP78 vaccines generated potent immunotherapeutic effects in a breast cancer mouse model. This novel strategy of targeting the GRP78 protein can promote the development of cancer vaccines and immunotherapies for breast cancer malignancies.