In the rapidly advancing field of cancer immunotherapy, a new way of looking at tumors has emerged, along with a new vocabulary for classifying and describing them. Read on to learn what the terms “hot” and “cold” mean as applied to solid tumors.Broadly speaking, cancer immunotherapy is an approach to treating cancer that works to retrain the body’s immune system so that it can better recognize and destroy cancer cells, which are so similar in appearance to healthy tissue that they are usually able to pass through the immune system’s defenses undetected and unchallenged. However, recent research has shown that some types of tumors are more likely than others to be engaged by the immune system.This is where the new vocabulary comes in. Researchers today talk about “hot” tumors as those with a higher potential for immune infiltration, while “cold” tumors are those with low levels of immune engagement. From a patient's perspective, this generally means that the hotter the tumor, the better. The belief is that the immune system stays engaged after a hot tumor is removed through surgery, so the probability of a relapse is much lower. The idea behind new therapies such as oncolytic viruses is therefore to turn cold tumors into hot ones.Researchers assess the “temperature” of tumors through a measure called the Immunoscore, which bases results on the density of two different T-cell types in a tumor sample. In at least one study so far conducted by Jerome Galon and his team at the Laboratory of Integrative Cancer Immunology in Paris, the Immunoscore was proven better at predicting the progression of cancer than other standard markers, such as pathological grade or tumor stage. While the study in question focused on colorectal cancer, the researchers believe that the concept should readily extend to other types of solid tumors.
In the last quarter of 2016, FierceBiotech included Oncorus on its Fierce 15 list of the year’s most promising biotech firms. FierceBiotech recognized the promise of Oncorus’ unique approach to immuno-oncology while honoring the organization’s commitment to making the therapy accessible. According to Mitchell Finer, one of the founders of Oncorus, the oncolytic virus being engineered by the firm can be manufactured at large scale and able to be shipped around the world.Currently, next-generation cancer treatments are limited to the American and European markets due in part to the expensive manufacturing methods that are employed. Offering the oncolytic virus globally could prove a game changer for markets across the world as a supplement to traditional treatment modalities, including radiation and chemotherapy. Finer also envisions multiple oncolytic virus products becoming available over the course of the next decade. Understanding that one size does not fit all for cancer treatment will allow Oncorus to engineer a range of treatments designed to target different solid tumors. By following the regulatory pathway of Imlygic, an oncolytic virus that already received approval from the FDA, Oncorus aims to see its first therapy, ONCR-001, gain approval and become available to patients as soon as possible.Oncorus is an immuno-oncology company based in Cambridge, Massachusetts. The company was launched in 2016 by MPM Capital with the launch team of Mitchell Finer, PhD as Chief Executive Officer and Thomas Chalberg, PhD MBA as Chief Operating Officer.
Oncorus, a biotechnology start-up based in Cambridge, MA, is engineering a novel way of fighting cancer using virus-based immunotherapies. The company’s oHSV platform makes use of the micro-RNAs found in healthy cells that are typically missing from the tumor microenvironment. These micro-RNAs play a key role in the regulation of protein synthesis and messenger-RNA degradation. Oncorus engineered micro-RNA binding sites into the viral genes of oHSV to make replication impossible in healthy cells. However, because these micro-RNAs are absent in tumor cells, oHSV can replicate and cause cell destruction. The oncolytic immunotherapy is injected into the tumor, where it triggers cell death and releases tumor antigens that trigger the natural immune response. As the virus continues to replicate, it disrupts the tumor microenvironment and spreads throughout the tumor while the immune system mounts an anti-tumor immune response. Oncorus oHSV is an ideal vector for oncolytic immunotherapy because it contains a high capacity for genes that can be engineered to carry a therapeutic payload. Oncorus has an active research program to engineer such a payload in its second-generation oHSV platform. These payloads have the ability to target specific immune modulators and proteases in the extracellular matrix to further bolster the immune response.
With hundreds of promising immunotherapies currently in development--like ONCR-001, the lead oncolytic virus candidate from Oncorus--it’s more important than ever for patients with cancer to consider participating in clinical trials. According to the Cancer Research Institute, only about 3 percent to 6 percent of eligible individuals take part in clinical trials for cancer therapies. This low participation rate slows down the clinical development process significantly, and means that valuable new treatments can take much longer to reach the people who need them.For patients who are thinking about participating in an immunotherapy clinical trial, the Cancer Research Institute offers some helpful information on how these treatments differ from other therapeutic approaches, and what prospective trial participants should look for. One of the most important things to understand is that immunotherapy is frequently used as a complement to or in combination with other treatments. This means that immunotherapy trials often require that patients be treated prior to or concurrently with the present standard of care. However, because immunotherapy does not have the same toxic side effects as conventional chemotherapies, participating in an immunotherapy trial may involve a lower degree of toxicity.In addition, prospective participants should be aware that, while immunotherapies are safe and have demonstrated significant potential for curing “incurable” cancers, there is still much that remains to be discovered about them. This means that immunotherapy trials may require a more intensive level of participation, such as more visits over a longer period, or a greater frequency of certain procedures. Furthermore, immunotherapies typically take longer to have an effect than other therapies.Patient participation in clinical trials is a key cornerstone of innovation to advance new therapies. Well-designed studies offer patients excellent care while allowing access to standard regimens in addition to the investigational product being studied.
Color blindness prevents over 10 million Americans from accurately distinguishing among certain primary colors, and at present there is no treatment or cure. The genetic disorder stems from a mutation on the X chromosome. Not only can it cause serious complications in everyday life, making tasks such as night driving more difficult, but it can also prevent people from pursuing certain career paths, such as aviation and electrical work. In early 2015, the medical research startup Avalanche Biotechnologies partnered with the University of Washington to improve upon a new gene therapy technique originally developed by Jay and Maureen Neitz, the lead researchers at the university’s Neitz Color Vision Lab. The couple has dedicated decades to advancing human health, and in 2009, they succeeded in curing color blindness in squirrel monkeys by surgically introducing new genes into the retina cells responsible for facilitating color vision. The team was eager to use their findings to help correct human vision, but the risk associated with their early-stage technique necessitated the development of a nonsurgical approach. In 2012, Jay and Maureen Neitz met Avalanche founder and then CEO Thomas Chalberg at a scientific conference. Dr. Chalberg’s firm had recently begun to optimize and commercialize a nonsurgical technique allowing for the delivery of genes via injection into the eye’s gelatinous vitreous layer. The three immediately set about collaborating to develop a genetic therapy for color blindness.
In 2015, Avalanche Biotechnologies, Inc., announced a partnership with the University of Washington in Seattle to develop genetically based treatments for color blindness. Using its proprietary platform, Ocular BioFactory, the Bay Area company collaborated with the university to explore innovations in the treatment of red-green color blindness, often categorized as CVD, or color vision deficiency. To further the project, two color vision experts from the university were scheduled to join the company’s scientific advisory panel. Avalanche also established a public education website, ColorVisionAwareness.com. The academic-corporate partnership sought to expand on UW research on gene therapies for color blindness, already detailed in a peer-reviewed article in the scientific publication Nature.About 10 million Americans are affected by color blindness, with males far outnumbering females. In fact, about 8 percent of males exhibit some form of color vision deficiency. Avalanche’s innovative BioFactory technology makes it possible to specifically target the human retina to deliver genetically modified virus components, which offer the opportunity to pioneer in the treatment of color blindness and other ophthalmologic conditions.
Due to the procedural rigor required by the medical and scientific communities, biotechnology companies face a unique set of challenges on the fundraising circuit. Here are three tips to help biotechnology entrepreneurs acquire funding for their business ventures. Focus on the science: In biotechnology, investors typically want to hear about the specific scientific proposition underlying the company. Entrepreneurs should always bring data to investor meetings and be honest about what they do and do not know. Balance youthful energy with experience: As with almost any other business, experienced leaders can add a great deal of value to a business. However, energy, passion, and youthful enthusiasm also plays a large role in a company’s ability to grow, recruit talent, and develop innovative solutions. Investors usually like to see both aspects in a biotechnology company.Research your investors: In many cases, biotechnology investors like to focus their activities on specific niches, including early stage, reformulations, and single asset plays. Consequently, entrepreneurs should research their investors and avoid wasting resources on deals that are unlikely to happen.
