Neoadjuvant administration of Semliki Forest virus expressing interleukin-12 combined with attenuated Salmonella eradicates breast cancer metastasis and achieves long-term survival in immunocompetent mice

BMC Cancer
M Gabriela KramerJosé A Chabalgoity

Abstract

Metastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer. 2×10(8) particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×10(7) units of an aroC (-) Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay. SFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90% of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not p...Continue Reading

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Citations

Jan 21, 2016·Immunotherapy·Ruben Hernandez-AlcocebaCristian Smerdou
Feb 24, 2018·Frontiers in Microbiology·M Gabriela KramerRobert M Hoffman
Apr 9, 2017·Expert Opinion on Drug Delivery·Zhaolu Xie, Xianghui Zeng
Feb 8, 2018·Frontiers in Immunology·Thais BascuasJosé A Chabalgoity
Jul 3, 2018·Oncology Letters·Tinglu LiHe Huang
Jul 24, 2020·International Journal of Molecular Sciences·Kenneth Lundstrom
Nov 13, 2020·Frontiers in Immunology·Khue G NguyenDavid A Zaharoff

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Methods Mentioned

BETA
surgical resection
ELISA

Software Mentioned

GraphPad Prism
Elements
NIS

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