Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8<sup>+</sup>T-cell functionality

Niavarani, Seyedeh-Raheleh; Lawson, Christine; Boudaud, Marie; Simard, Camille; Tai, Lee-Hwa

doi:10.1136/jitc-2019-000465

Cited by 36 publications

(32 citation statements)

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“…Oncolytic viruses (OV) transform immunotherapy from a sterile immunity to a pathogen-associated-like immunity, as these viruses replicate preferentially in tumor cells and release TAAs and PAMPS [ 132 , 133 ]. In this emerging in situ vaccination strategy in breast cancer models, pox- [ 134 , 135 ], reo- [ 136 ], herpes simplex [ 137 , 138 , 139 ], adeno- [ 140 , 141 , 142 , 143 ], Newcastle disease [ 144 , 145 ], Vesicular stomatitis [ 146 ], and measles [ 147 , 148 , 149 ] viruses have been employed to make breast tumors more immunogenic and more responsive to immunotherapies by priming the TME to signs of infection and releasing TAAs [ 150 ]. Moreover, these viruses can be engineered to express various TAAs to further prime an immunological response from TME.…”

Section: Oncolytic Virusesmentioning

confidence: 99%

“…Moreover, these viruses can be engineered to express various TAAs to further prime an immunological response from TME. In the last couple years, the field of oncolytic viruses in BC models has been burgeoning and opened new avenues for combination immunotherapies, such as vaccines [ 146 , 151 ], suppressor cell targeting [ 152 ], and checkpoint inhibitors [ 134 , 140 , 146 , 150 , 152 , 153 , 154 , 155 , 156 ]. Moreover, several BC clinical trials are currently ongoing (see Table 2 ).…”

Section: Oncolytic Virusesmentioning

confidence: 99%

“…Niavarani, et al have recently employed an autologous 4T1 cell vaccine (inactivated by gamma-irradiation) infected with Recombinant Vesicular Stomatitis Virus (VSVd51) [ 146 ]. The vaccine was injected subcutaneously in TNBC models using MDA-MB-231, BT-549, and 4T1 TNBC cell lines.…”

Section: Oncolytic Virusesmentioning

confidence: 99%

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The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

Gordon

Gadi

2020

Vaccines

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Breast cancer affects roughly one in eight women over their lifetime and is a leading cause of cancer-related death in women. While outcomes have improved in recent years, prognosis remains poor for patients who present with either disseminated disease or aggressive molecular subtypes. Cancer immunotherapy has revolutionized the treatment of several cancers, with therapeutic vaccines aiming to direct the cytotoxic immune program against tumor cells showing particular promise. However, these results have yet to translate to breast cancer, which remains largely refractory from such approaches. Recent evidence suggests that the breast tumor microenvironment (TME) is an important and long understudied barrier to the efficacy of therapeutic vaccines. Through an improved understanding of the complex and biologically diverse breast TME, it may be possible to advance new combination strategies to render breast carcinomas sensitive to the effects of therapeutic vaccines. Here, we discuss past and present efforts to advance therapeutic vaccines in the treatment of breast cancer, the molecular mechanisms through which the TME contributes to the failure of such approaches, as well as the potential means through which these can be overcome.

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Section: Oncolytic Virusesmentioning

confidence: 99%

Section: Oncolytic Virusesmentioning

confidence: 99%

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The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

Gordon

Gadi

2020

Vaccines

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“…RNA viruses including vesicular stomatitis virus (VSV), Newcastle disease virus (NDV), reovirus and Maraba virus have also been studied for their oncolytic activities against BrCa. Niavarani et al [59] used an oncolytic VSV to infect inactivated tumor cells (ICV) and used those infected cells as a vaccine against TNBC. Compared to the ICV alone, VSV-infected ICV resulted in much better protection in the 4T1 tumor model.…”

Section: Replicating Viruses For Breast Cancer Therapymentioning

confidence: 99%

Viroimmunotherapy for breast cancer: promises, problems and future directions

Chaurasiya

Fong

2020

Cancer Gene Ther

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Virotherapy, a strategy to use live viruses as therapeutics, is a relatively novel field in the treatment of cancer. With the advancements in molecular biology and virology, there has been a huge increase in research on cancer virotherapy. For the treatment of cancer, viruses could be used either as vectors in gene therapy or as oncolytic agents. A variety of viruses have been studied for their potential usage in gene therapy or oncolytic therapy. In this review, we discuss virotherapy with a special focus on breast cancer. Breast cancer is the most common cancer and the leading cause of cancer-related deaths in women worldwide. Current treatments are insufficient to cure metastatic breast cancer and are often associated with severe side effects that further deteriorates patients' quality of life. Therefore, novel therapeutic approaches such as virotherapy need to be developed for the treatment of breast cancer. Here we summarize the current treatments for breast cancer and the potential use of virotherapy in the treatment of the disease. Furthermore, we discuss the use of oncolytic viruses as immunotherapeutics and the rational combination of oncolytic viruses with other therapeutics for optimal treatment of breast cancer. Finally, we outline the progress made in virotherapy for breast cancer and the shortcomings that need to be addressed for this novel therapy to move to the clinic for better treatment of breast cancer.

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“…Moreover, the efficacy of ICV is improved when combined with checkpoint blockade (anti-PD-1). 3 Our goal is to further improve ICV by applying a prime-boost cancer vaccination strategy to further enhance anti-tumor immune responses in preclinical and translational studies. 4 5 Methods We will choose the best 'prime vaccine' based on the immunogenicity of TNBC cell lines after treatment with immunomodulators such as chemotherapeutic agents, irradiation, toll-like receptor agonists and anti-viral vaccines.…”

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confidence: 99%

848 Prime-boost vaccination for the treatment of triple negative breast cancer

Niavarani

Lawson

Tai

2020

Late-Breaking Abstracts

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BackgroundTriple negative breast cancer (TNBC) is currently only treated with surgery and chemotherapy.1 TNBC has higher rates of genetic mutations and contains more tumor infiltrating lymphocytes.2 These characteristics provide a strong rationale to use novel immunotherapies such as immunogenic autologous tumor cell vaccines to therapeutically target TNBC. We have demonstrated that an infected cell vaccine (ICV) that is made from irradiated and oncolytic virus tumor infected cells induces beneficial innate and adaptive immune responses in a syngeneic mouse model of TNBC. Moreover, the efficacy of ICV is improved when combined with checkpoint blockade (anti-PD-1).3 Our goal is to further improve ICV by applying a prime-boost cancer vaccination strategy to further enhance anti-tumor immune responses in preclinical and translational studies.4 5MethodsWe will choose the best ‘prime vaccine’ based on the immunogenicity of TNBC cell lines after treatment with immunomodulators such as chemotherapeutic agents, irradiation, toll-like receptor agonists and anti-viral vaccines. We will measure the release of damage-associated molecular patterns (DAMPs), which act as danger signals to initiate tumor-targeted immune responses,6 after the treatment of TNBC cell lines. We will test the polarization of human monocytes when co-cultured with conditioned media (CM) from treated TNBC cells. We will also analyze the migration of human immune cells (CD56+NK cells and CD8+T cells) toward the CM of treated human TNBC cells. Furthermore, we will evaluate the maturation markers on CD11C+ dendritic (DC) cells differentiated from mouse bone marrow cells when co-cultured with the cell lysate of the mouse TNBC cell line treated with ‘prime vaccine’ candidates. For in vivo studies, we will test our best prime vaccine followed by the ICV as a boost vaccine in our BALB/c-4T1 mouse model. We will analyze the cytotoxicity of T lymphocytes and the secretion of cytokines, and overall survival.ResultsFrom measuring DAMP levels and analyzing immune functions, our preliminary results suggest that oxaliplatin and the seasonal influenza vaccine are the best candidates as strong ‘prime vaccine’ candidates compared to other treatments. DCs differentiated from isolated bone marrow cells exhibited a higher percentage of markers of maturation when co-cutured ex vivo with cell lysate of 4T1 cells were treated with oxaliplatin compared to control groups. In vivo studies in the BALB/c-4T1 model have begun to test the best prime-boost vaccine combinations.ConclusionsThese results demonstrate the therapeutic potential of oncolytic virus-based immunogenic tumor vaccines could be improved by applying the ‘prime-boost’ cancer vaccination approach to treat TNBC.Ethics Approval‘The study was approved by the CRCHUS Human Ethics Board, approval number 2018-2414.’Consent‘Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.’ReferencesYadav BS. Systemic treatment strategies for triple-negative breast cancer. World J Clin Oncol 2014;5(2):125.García-Teijido P, Cabal ML, Fernández IP, Pérez YF. Tumor-infiltrating lymphocytes in triple negative breast cancer: the future of immune targeting. Clinical Medicine Insights: Oncology 2016.Niavarani SR, Lawson C, Boudaud M, Simard C, Tai LH. Oncolytic vesicular stomatitis virus-based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8 + T-cell functionality. J Immunother Cancer 2020.Le DT, et al. Safety and survival with GVAX pancreas prime and listeria monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol 2015.Pol JG, et al. Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic maraba virus currently in first-in-human trials. Oncoimmunology 2019 Jan;8(1):e1512329.Vandenberk L, Belmans J, Van Woensel M, Riva M, Van Gool SW. Exploiting the immunogenic potential of cancer cells for improved dendritic cell vaccines. Frontiers in Immunology 2016.

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Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8⁺T-cell functionality

Cited by 36 publications

References 47 publications

The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

Viroimmunotherapy for breast cancer: promises, problems and future directions

848 Prime-boost vaccination for the treatment of triple negative breast cancer

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Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8+T-cell functionality

Cited by 36 publications

References 47 publications

The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

The Role of the Tumor Microenvironment in Developing Successful Therapeutic and Secondary Prophylactic Breast Cancer Vaccines

Viroimmunotherapy for breast cancer: promises, problems and future directions

848 Prime-boost vaccination for the treatment of triple negative breast cancer

Contact Info

Product

Resources

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Oncolytic vesicular stomatitis virus–based cellular vaccine improves triple-negative breast cancer outcome by enhancing natural killer and CD8⁺T-cell functionality