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Retargeted and Multi-cytokine-Armed Herpes Virus Is a Potent Cancer Endovaccine for Local and Systemic Anti-tumor Treatment
- Source :
- Molecular Therapy: Oncolytics, Vol 19, Iss, Pp 253-264 (2020), Molecular Therapy Oncolytics
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Oncolytic viruses (OVs) are novel anti-tumor agents with the ability to selectively infect and kill tumor cells while sparing normal tissue. Beyond tumor cytolysis, OVs are capable of priming an anti-tumor immune response via lysis and cross-presentation of locally expressed endogenous tumor antigens, acting as an “endovaccine.” The effectiveness of OVs, similar to other immunotherapies, can be hampered by an immunosuppressive tumor microenvironment. In this study, we modified a previously generated oncolytic herpes simplex virus (oHSV) retargeted to the human HER2 (hHER2) tumor molecule and encoding murine interleukin-12 (mIL-12), by insertion of a second immunomodulatory molecule, murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), to maximize therapeutic efficacy. We assessed the efficacy of this double-armed virus (R-123) compared to singly expressing GM-CSF and IL-12 oHSVs in tumor-bearing mice. While monotherapies were poorly effective, combination with α-PD1 enhanced the anti-tumor response, with the highest efficacy of 100% response rate achieved by the combination of R-123 and α-PD1. Efficacy was T cell-dependent, and the induced immunity was long lasting and able to reject a second contralateral tumor. Importantly, systemic delivery of R-123 combined with α-PD1 was effective in inhibiting the development of tumor metastasis. As such, this approach could have a significant therapeutic impact paving the way for further development of this platform in cancer immunotherapy.<br />Graphical Abstract<br />Fully virulent tumor retargeted HSV oncolytic viruses (THVs) are novel immunotherapeutic agents with increased specificity, safety, and potency. De Lucia et al. propose the use of a hHER2 THV expressing IL-12 and GM-CSF as a strategy to potentiate anti-tumor efficacy in combination with anti-PD1, opening future perspectives for local and systemic treatment.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_treatment
medicine.disease_cause
lcsh:RC254-282
Virus
Metastasis
03 medical and health sciences
0302 clinical medicine
Immune system
Cancer immunotherapy
medicine
cytokine
cancer
Pharmacology (medical)
immune checkpoint
retargeted Herpes virus
oncolytic virus
Tumor microenvironment
business.industry
GM-CSF
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Immune checkpoint
cytokines
Oncolytic virus
030104 developmental biology
Herpes simplex virus
Oncology
oncolytic viru
IL-12
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Original Article
business
endovaccine
Subjects
Details
- Language :
- English
- ISSN :
- 23727705
- Volume :
- 19
- Database :
- OpenAIRE
- Journal :
- Molecular Therapy: Oncolytics
- Accession number :
- edsair.doi.dedup.....33e0ff896c974912e12b86497d6ded08