Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics

Autor: Binfeng Lu, Walter J. Storkus, Yukai He, Enyong Dai, David L. Bartlett, Zuqiang Liu, Zongbi Guo, Weilin Liu, Zong Sheng Guo, Mathilde Feist, Esther Giehl
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
T-Lymphocytes
medicine.medical_treatment
Genetic Vectors
Immunology
Vaccinia virus
Review
Cancer Vaccines
lcsh:RC254-282
03 medical and health sciences
0302 clinical medicine
Cancer immunotherapy
Neoplasms
medicine
Animals
Humans
Immunology and Allergy
Oncolytic Virotherapy
Pharmacology
Membrane Glycoproteins
business.industry
Clinical Studies as Topic
Cancer
Dendritic Cells
Genetic Therapy
Immunotherapy
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Metastatic breast cancer
Immune checkpoint
3. Good health
Oncolytic virus
Oncolytic Viruses
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Host-Pathogen Interactions
Cancer research
Molecular Medicine
Immunogenic cell death
Cancer vaccine
Genetic Engineering
business
Zdroj: Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-21 (2019)
Journal for Immunotherapy of Cancer
ISSN: 2051-1426
DOI: 10.1186/s40425-018-0495-7
Popis: Cancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with advanced-stage cancer. In particular, recombinant vaccinia viruses (VV) hold great promise as interventional agents. In this article, we first summarize the current understanding of virus biology and viral genes involved in host-virus interactions to further improve the utility of these agents in therapeutic applications. We then discuss recent findings from basic and clinical studies using VV as cancer vaccines and oncolytic immunotherapies. Despite encouraging results gleaned from translational studies in animal models, clinical trials implementing VV vectors alone as cancer vaccines have yielded largely disappointing results. However, the combination of VV vaccines with alternate forms of standard therapies has resulted in superior clinical efficacy. For instance, combination regimens using TG4010 (MVA-MUC1-IL2) with first-line chemotherapy in advanced-stage non-small cell lung cancer or combining PANVAC with docetaxel in the setting of metastatic breast cancer have clearly provided enhanced clinical benefits to patients. Another novel cancer vaccine approach is to stimulate anti-tumor immunity via STING activation in Batf3-dependent dendritic cells (DC) through the use of replication-attenuated VV vectors. Oncolytic VVs have now been engineered for improved safety and superior therapeutic efficacy by arming them with immune-stimulatory genes or pro-apoptotic molecules to facilitate tumor immunogenic cell death, leading to enhanced DC-mediated cross-priming of T cells recognizing tumor antigens, including neoantigens. Encouraging translational and early phase clinical results with Pexa-Vec have matured into an ongoing global phase III trial for patients with hepatocellular carcinoma. Combinatorial approaches, most notably those using immune checkpoint blockade, have produced exciting pre-clinical results and warrant the development of innovative clinical studies. Finally, we discuss major hurdles that remain in the field and offer some perspectives regarding the development of next generation VV vectors for use as cancer therapeutics.
Databáze: OpenAIRE
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