Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Dec 20, 2018; 9(8): 188-199
Published online Dec 20, 2018. doi: 10.5306/wjco.v9.i8.188
Combination immunotherapy with Survivin and luteinizing hormone-releasing hormone fusion protein in murine breast cancer model
Himani Garg, Rohit Singh Hada, Jagdish C Gupta, G P Talwar, Shweta Dubey
Himani Garg, Rohit Singh Hada, Jagdish C Gupta, G P Talwar, Talwar Research Foundation, Neb Sarai, New Delhi 110068, India
Himani Garg, Shweta Dubey, Amity Institute of Virology and Immunology, Amity University Uttar Pradesh, Noida 201303, Uttar Pradesh, India
Author contributions: Gupta JC and Dubey S shared corresponding authorship; Garg H and Hada RS conducted and analysed the experiments; Gupta JC and Dubey S designed the study and wrote the manuscript; Talwar GP edited the manuscript.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Amity Institute of Pharmacy, Amity University, Noida, UP, India (IACUC protocol number: AIP/CPSCEA/PRO/01/2015).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author to: Shweta Dubey, PhD, Associate Professor, Amity Institute of Virology and Immunology, Amity University Uttar Pradesh, J-3 Block, Room No: LG21, Sector 125, Noida 201303, Uttar Pradesh, India. sdubey@amity.edu
Telephone: +91-120-4586865 Fax: +91-120-4392320
Received: June 16, 2018
Peer-review started: June 17, 2018
First decision: July 19, 2018
Revised: August 24, 2018
Accepted: November 4, 2018
Article in press: November 4, 2018
Published online: December 20, 2018
Abstract
AIM

To investigate the therapeutic potential of two recombinant proteins, Survivin and luteinizing hormone-releasing hormone (LHRH) fusion protein [LHRH(6leu)-LTB] for immunotherapy of breast cancer.

METHODS

Murine 4T-1 breast cancer model was used to evaluate the efficacy of recombinant proteins in vivo. Twenty four Balb/c mice were divided into 4 groups of 6 mice each. Recombinant Survivin and LHRH fusion protein, alone or in combination, were administered along with immunomodulator Mycobacterium indicus pranii (MIP) in Balb/c mice. Unimmunized or control group mice were administered with phosphate buffer saline. Each group was then challenged with syngeneic 4T-1 cells to induce the growth of breast tumor. Tumor growth was monitored to evaluate the efficacy of immune-response in preventing the growth of cancer cells.

RESULTS

Preventive immunization with 20 µg recombinant Survivin and MIP was effective in suppressing growth of 4T-1 mouse model of breast cancer (P = 0.04) but 50 µg dose was ineffective in suppressing tumor growth. However, combination of Survivin and LHRH fusion protein was more effective in suppressing tumor growth (P = 0.02) as well as metastasis in vivo in comparison to LHRH fusion protein as vaccine antigen alone.

CONCLUSION

Recombinant Survivin and MIP suppress tumor growth significantly. Combining LHRH fusion protein with Survivin and MIP enhances tumor suppressive effects marginally which provides evidence for recombinant Survivin and LHRH fusion protein as candidates for translating the combination cancer immunotherapy approaches.

Keywords: Immunotherapy, Survivin, Luteinizing hormone-releasing hormone fusion protein, Combination immunotherapy, Breast cancer

Core tip: Targeting Survivin for treatment of cancer is an emerging trend in cancer immunotherapy. In this study we optimized the dose of recombinant full-length Survivin for tumor growth inhibition. Since luteinizing hormone-releasing hormone (LHRH) is also known to support breast cancer in case of premenopausal women, we combined recombinant LHRH fusion protein with Survivin and Mycobacterium indicus pranii and obtained a positive anti-tumor response. We report our results of using recombinant Survivin protein and LHRH fusion protein as potential vaccine antigens for immunotherapy of murine model of breast cancer which was developed by injecting 4T-1 mammary cell line in syngeneic Balb/c mice. Immunized mice challenged with syngeneic 4T-1 cells exhibited suppression of tumor growth and metastasis in lungs in comparison to control mice.