Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

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New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

Current Medicinal Chemistry ◽

10.2174/0929867324666170830094922 ◽

2018 ◽

Vol 25 (36) ◽

pp. 4758-4784 ◽

Cited By ~ 8

Author(s):

Amy L. Wilson ◽

Magdalena Plebanski ◽

Andrew N. Stephens

Keyword(s):

Clinical Trials ◽

Cell Death ◽

Immune System ◽

Cancer Therapy ◽

Immune Cell ◽

Cytotoxic T Lymphocyte ◽

Tumour Microenvironment ◽

Immune Checkpoints ◽

Tumour Regression ◽

Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

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Laser nanobubbles induce immunogenic cell death in breast cancer

Nanoscale ◽

10.1039/d0nr06587k ◽

2021 ◽

Vol 13 (6) ◽

pp. 3644-3653

Author(s):

Hieu T. M. Nguyen ◽

Nitesh Katta ◽

Jessica A. Widman ◽

Eri Takematsu ◽

Xu Feng ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Dendritic Cell ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Cell Activation ◽

Immunogenic Cell Death ◽

Dendritic Cell Activation

Laser nanobubbles induce dendritic cell activation in breast cancer cells.

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Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001684 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001684

Author(s):

Rafael Moreno

Keyword(s):

Stem Cells ◽

Clinical Trials ◽

Mesenchymal Stem Cells ◽

Immune System ◽

Oncolytic Viruses ◽

Immunogenic Cell Death ◽

The Past ◽

Physical Barriers ◽

Immunogenic Properties ◽

New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

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Autocrine Growth Hormone (GH)-Mediated Triptolide Resistance Overcame by Metformin Co-Treatment in MDA-MB231 Breast Cancer Cells Through ER Stress Pathway

Proceedings ◽

10.3390/proceedings2019040009 ◽

2019 ◽

Vol 40 (1) ◽

pp. 9

Author(s):

Amani Abdulmunem ◽

Pınar Obakan-Yerlikaya ◽

Elif-Damla Arisan ◽

Ajda Coker-Gurkan

Keyword(s):

Breast Cancer ◽

Growth Hormone ◽

Cell Death ◽

Er Stress ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Autocrine Growth ◽

Common Cancer

Breast cancer is the most common cancer in women worldwide and the second most common cancer overall. Autocrine growth hormone (GH) expression induced cell proliferation, growth, invasion-metastasis in vitro and in vivo breast cancer models. Moreover, forced GH signaling acts as a drug resistance profile in breast cancer cell lines against chemotherapeutic drugs such as tamoxifen, mitomycin C, doxorubicin and curcumin. Triptolide, an active plant extract from Tripterygium wilfordii, has been shown to induce apoptotic cell death in various cancer cells such a prostate, colon, breast cancer. Metformin, a common therapeutic agent for type II Diabetes mellitus, has been shown to induce autophagy, endoplasmic reticulum (ER) stress and apoptotic cell death in cancer cells. Our aim is to demonstrate the potential effect of metformin on triptolide-mediated drug resistance in autocrine GH expressing MDA-MB-231 breast cancer cells through Endoplasmic reticulum (ER) stress. Autocrine GH-mediated triptolide (20 nM) resistance overcame by metformin (2 mM) co-teatment in MDA-MB231 breast cancer cells through accelerating cell viability loss, growth inhibition compared to alone triptolide treatment. Combined treatment increased apoptotic cell death via CHOP activation, IRE1α upregulation. Consequently, we suggest that triptolide can be more effective with metformin combination in MDA-MB-231 GH+ drug resistant breast cancer cells.

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