“Re-engineering a common cold virus to attack the deadliest kind of brain tumor extended the survival of patients whose tumor returned after various treatments, including surgery, a Phase 1 clinical trial shows.
“While patients with glioblastoma usually live a median of six months, half were still alive at 9/12 months after receiving the re-engineered virus. And 20 percent lived for three years or longer.”
“The combination of an oncolytic virus plus a checkpoint inhibitor improved survival among patients with advanced melanoma compared with monotherapy, according to data from a phase 2 study published in Journal of Clinical Oncology.
“Novel monotherapies, such as ipilimumab (Yervoy, Bristol-Myers Squibb) — a CTLA-4 antibody — have ‘transformed patient care in advanced melanoma,’ the researchers wrote.”
“Immunotherapy is a promising approach in the treatment of metastatic melanoma, an aggressive and deadly form of skin cancer; but for most patients, immunotherapy drugs so far have failed to live up to their promise and provide little or no benefit. In a phase 1b clinical trial with 21 patients, researchers tested the safety and efficacy of combining the immunotherapy drug pembrolizumab with an oncolytic virus called T-VEC. The results suggest that this combination treatment, which had a 62% response rate, may work better than using either therapy on its own. The study appears September 7 in the journal Cell.”
“The addition of T-VEC (T-VEC; Imlygic), a herpes simplex virus 1-based oncolytic virus, to CTLA-4 inhibitor ipilimumab (Yervoy) improves the objective response rate (ORR) in patients with unresected stage IIIb to IV melanoma, according to findings presented at the 7th European Post-Chicago Melanoma/Skin Cancer Meeting.
“T-VEC was the first approved oncolytic virus therapy in Europe, the United States, and Australia, and its efficacy was previously demonstrated in a phase III trial comprising patients with advanced unresectable melanoma.”
There are many hopes that combining immune checkpoint inhibitor drugs, or combining them with drugs of other types (immunotherapy, targeted therapy, or chemotherapy) is the future of treatment for many kinds of cancer. Literally hundreds of clinical trials are actively exploring these combinations, and melanoma is the cancer for which trials of this type abound. Last month, the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago featured just a few presentations in this area, apparently because it is too early to report results from the many ongoing trials with drug combinations. Continue reading…
With a few exceptions, glioblastoma (GBM) remains largely incurable, and the U.S. Food and Drug Administration (FDA) has approved few treatments for the disease. Surgery (when feasible), radiation, and temozolomide are used in most patients. But even if a newly diagnosed tumor can be surgically excised, recurrences are too common.
In this blog post, I simply list some of the new treatments available in clinical trials for GBM and other high-grade brain tumors. Only drugs that have at least some preliminary results of activity are included, and the list is not meant to be fully comprehensive. The interested reader can judge for herself what might be of interest, keeping in mind that no single treatment is suitable or will work for all GBM patients. Continue reading…
“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.”
“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.
Le Bœuf F, Batenchuk C, Vähä-Koskela M, Breton S, et al. Nature Communications. Jun 14, 2013.
“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.”