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Bioimpacts. 2024;14(2): 27829.
doi: 10.34172/bi.2023.27829
  Abstract View: 585
  PDF Download: 347

Original Article

Introduction of a new recombinant vaccine based on GRP78 for breast cancer immunotherapy and evaluation in a mouse model

Hamed Zare 1 ORCID logo, Hamid Bakherad 2,3* ORCID logo, Arman Nasr Esfahani 2, Mohamad Norouzi 2, Hossein Aghamollaei 4, Seyed Latif Mousavi Gargari 5, Fatemeh Mahmoodi 6, Mahdi Aliomrani 7, Walead Ebrahimizadeh 8

1 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
*Corresponding Author: Hamid Bakherad, , Email: bakheradh@pharm.mui.ac.ir

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.
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Submitted: 01 Mar 2023
Revision: 04 Jul 2023
Accepted: 29 Jul 2023
ePublished: 18 Sep 2023
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