Immunotherapy Combination Promising in Advanced Melanoma

Excerpt:

“Combination treatment with an intratumoral injection of Coxsackievirus A21 (CVA21) and the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab has demonstrated durable response with minimal toxicity among patients with advanced melanoma, according to data (abstract CT114) presented at the American Association for Cancer Research (AACR) Annual Meeting 2017, held April 1–5 in Washington, DC.

“Response to the combination occurred even among several patients whose melanoma had progressed despite prior treatment with an immune checkpoint inhibitor.”

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ASCO Immunotherapy Preview: These Cancer-Killing Viruses May Save Lives

“The closely watched annual meeting of the American Society of Clinical Oncology (ASCO) is about to kick off in Chicago, and if the last few years are any indication, immunotherapy will likely steal the show. Cancer researchers have been perfecting all sorts of ways to stimulate patients’ immune systems to fight cancer, from chimeric antigen receptor T-cells (CARTs) now being tested in blood cancers, to ‘checkpoint inhibitors’ like Bristol-Myers Squibb’s blockbuster melanoma treatment Yervoy (ipilimumab). But this year, an up-and-coming class of immune-boosting drugs could draw attention at ASCO—viruses that are specially engineered so they destroy tumors and then prime patients’ immune systems to continue fighting off their cancer.

“Virus-based cancer treatments, sometimes referred to as ‘virotherapy,’ constitute a fast-growing niche within immunotherapy, and one that is generating a tremendous amount of excitement in the oncology world this year. The idea has actually been around since the late 1800s, when physicians first realized that some viruses have a natural ability to kill cancer cells. But these so-called oncolytic viruses didn’t start breaking out until recently, as advances in genetic engineering have made it feasible to manipulate the virus’ genomes—recreating them, if you will, into supercharged cancer-killing machines that attack tumors but leave normal tissues alone.”


World First as Viral Immunotherapy for Skin Cancer Shows Patient Benefit in Phase III Trial

“A genetically engineered herpes virus can halt the progression of skin cancer by killing cancer cells and sparking the immune system into action against tumours, a landmark clinical trial has shown.

“It is the first time that a phase III trial of viral immunotherapy has definitively shown benefit for patients with cancer.

“The trial was led in the UK by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and involved 64 research centres worldwide including the University of Oxford.

“Researchers randomised 436 patients with aggressive, inoperable malignant melanoma to receive either an injection of the viral therapy, called Talimogene Laherparepvec, or a control immunotherapy.”


Targeted Virus Could Boost Chemo's Effects for Arm and Leg Cancer

Virus“Patients with cancer of the arms and legs often undergo chemotherapy to avoid amputation. Now, researchers from The Institute of Cancer Research in London, UK, say that viruses designed to target and then kill cancer cells could increase the effectiveness of these chemotherapy treatments.

“As an alternative to amputation, the type of chemotherapy such cancer patients undergo is called isolated limb perfusion chemotherapy, which is given directly to blood vessels that supply the affected arm or leg.

“The technique allows high-dose chemotherapy drugs to target the affected limb without blasting the body with toxic chemicals. To do this, a heart and lung bypass machine is connected to the arm or leg to separate its blood supply from the rest of the body.

“But the researchers, who publish their findings in the International Journal of Cancer, tested the effectiveness of using a genetically engineered version of the virus used for smallpox vaccination alongside this chemotherapy.

“The virus, known as GLV-1h68, was modified to infect and kill cancer cells, the team explains, adding that the virus alongside isolated limb perfusion chemotherapy was more effective in rats than either of the treatments on their own.

“If these results are successful in the clinic, the researchers say the combination of the two could help certain skin cancer and sarcoma patients avoid major surgery or amputation.

“Approval for a clinical trial to test the combination treatment in cancer patients has now been approved and will take place at some point soon.”


Infecting Just One Tumor with a Virus Could Boost the Systemic Effectiveness of Cancer Immunotherapy

“A Ludwig Cancer Research study suggests that the clinical efficacy of checkpoint blockade, a powerful new strategy to harness the immune response to treat cancers, might be dramatically improved if combined with oncolytic virotherapy, an investigational intervention that employs viruses to destroy tumors.

“Published today in the journal Science Translational Medicine, the study evaluated a combination therapy in which the Newcastle disease virus (NDV), a bird virus not ordinarily harmful to humans, is injected directly into one of two melanoma tumors implanted in mice, followed by an antibody that essentially releases the brakes on the immune response. The researchers report that the combination induced a potent and systemically effective anti-tumor immune response that destroyed the non-infected tumor as well. Even tumor types that have hitherto proved resistant to checkpoint blockade and other immunotherapeutic strategies were susceptible to this combined therapy.”

Editor’s Note: This story is about research that was performed in mice. For that reason, we cannot assume that similar results would happen for humans. However, viruses like the one explored here are already being used in people. To learn more about immunotherapy—cancer treatments that use the immune system to fight tumors—visit our Melanoma Basics.


The Landscape of Viral Expression and Host Gene Fusion and Adaptation in Human Cancer

“Viruses cause 10–15% of all human cancers. Massively parallel sequencing has recently proved effective for uncovering novel viruses and virus–tumour associations, but this approach has not yet been applied to comprehensive patient cohorts. Here we screen a diverse landscape of human cancer, encompassing 4,433 tumours and 19 cancer types, for known and novel expressed viruses based on >700 billion transcriptome sequencing reads from The Cancer Genome Atlas Research Network. The resulting map confirms and extends current knowledge. We observe recurrent fusion events, including human papillomavirus insertions in RAD51B and ERBB2. Patterns of coadaptation between host and viral gene expression give clues to papillomavirus oncogene function. Importantly, our analysis argues strongly against viral aetiology in several cancers where this has frequently been proposed. We provide a virus–tumour map of unprecedented scale that constitutes a reference for future studies of tumour-associated viruses using transcriptome sequencing data.”


The Landscape of Viral Expression and Host Gene Fusion and Adaptation in Human Cancer

“Viruses cause 10–15% of all human cancers. Massively parallel sequencing has recently proved effective for uncovering novel viruses and virus–tumour associations, but this approach has not yet been applied to comprehensive patient cohorts. Here we screen a diverse landscape of human cancer, encompassing 4,433 tumours and 19 cancer types, for known and novel expressed viruses based on >700 billion transcriptome sequencing reads from The Cancer Genome Atlas Research Network. The resulting map confirms and extends current knowledge. We observe recurrent fusion events, including human papillomavirus insertions in RAD51B and ERBB2. Patterns of coadaptation between host and viral gene expression give clues to papillomavirus oncogene function. Importantly, our analysis argues strongly against viral aetiology in several cancers where this has frequently been proposed. We provide a virus–tumour map of unprecedented scale that constitutes a reference for future studies of tumour-associated viruses using transcriptome sequencing data.”


The Landscape of Viral Expression and Host Gene Fusion and Adaptation in Human Cancer

“Viruses cause 10–15% of all human cancers. Massively parallel sequencing has recently proved effective for uncovering novel viruses and virus–tumour associations, but this approach has not yet been applied to comprehensive patient cohorts. Here we screen a diverse landscape of human cancer, encompassing 4,433 tumours and 19 cancer types, for known and novel expressed viruses based on >700 billion transcriptome sequencing reads from The Cancer Genome Atlas Research Network. The resulting map confirms and extends current knowledge. We observe recurrent fusion events, including human papillomavirus insertions in RAD51B and ERBB2. Patterns of coadaptation between host and viral gene expression give clues to papillomavirus oncogene function. Importantly, our analysis argues strongly against viral aetiology in several cancers where this has frequently been proposed. We provide a virus–tumour map of unprecedented scale that constitutes a reference for future studies of tumour-associated viruses using transcriptome sequencing data.”


Model-Based Rational Design of an Oncolytic Virus with Improved Therapeutic Potential

“Oncolytic viruses are complex biological agents that interact at multiple levels with both tumour and normal tissues. Antiviral pathways induced by interferon are known to have a critical role in determining tumour cell sensitivity and normal cell resistance to infection with oncolytic viruses. Here we pursue a synthetic biology approach to identify methods that enhance antitumour activity of oncolytic viruses through suppression of interferon signalling. On the basis of the mathematical analysis of multiple strategies, we hypothesize that a positive feedback loop, established by virus-mediated expression of a soluble interferon-binding decoy receptor, increases tumour cytotoxicity without compromising normal cells.”