Release date: 2015-12-09

In the past few decades, artificially improving the body's immune response against cancer has become the most exciting breakthrough in cancer treatment. But at a recent scientific conference in New York, the full agenda shows that there are still many issues that need to be resolved before the war for humanity to fight cancer is finally won. For example: What is the best way to drive the immune system? Does immunotherapy work for a variety of cancer patients or can it target only a few lucky people? Is there a way to make immunotherapy safer and less expensive?

At the first International Conference on Cancer Immunotherapy held on September 16-19, many reports were packed and many listeners could only stand. One speaker after another made a speech. At the beginning of the report, they always disclosed their research and financial links with commercial companies. These companies range from pharmaceutical giants to startups run by researchers themselves. The audience is mainly scientists and doctors. But among the 1,400 participants, in addition to a few reporters, there are a large number of industry investigators and financial professionals who are trying to collect the next big investment opportunity or possible cooperation project.

Jill O'Donnell-Tormey, CEO of the Cancer Research Institute, claims that 2015 is "a truly significant year for cancer immunotherapy." The US Food and Drug Administration has approved two new immunotherapeutics, she said: "More than half of current cancer clinical trials include some form of immunotherapy." Some teams are studying possible combination therapies, while global Oncologists realize that "a paradigm shift is taking place in cancer research." Despite these exhilarating advances, she added: "However, from the perspective of understanding and fully applying this approach, we are just standing at the starting point. ”

Current status of cancer immunotherapy
The first thing you need to know about researchers working on cancer immunotherapy is that each of them seems to have several surprisingly good cases. Steven Rosenberg of the National Cancer Institute is undoubtedly the best of these people. In 1984, he treated a woman named Linda Taylor who had metastatic melanoma (a malignant skin cancer with a 10-year survival rate of less than 10%). Taylor was the 81st patient to receive treatment, but it was the first successful case. Her tumor disappeared in just a few months, and she still lives alive today. Rosenberg, the conference's keynote speaker, mentioned in his report that his latest program will not cause great pain to patients, and 20% of patients experience "a complete and lasting relief." This is similar to the immunotherapy in many studies.

The second thing you need to know is that in most cases the body is trying to suppress the immune response for a reason. The immune system has a very powerful weapon in its arsenal, so that it can kill people more quickly than any disease. Doctors mobilize the immune system to treat cancer, as well as chemotherapy and radiotherapy, with strong side effects. (In fact, for more complex reasons, some immunotherapy requires a certain dose of chemotherapy or radiation in the first step.) As Rosenberg puts it, “Based on research practices in this field and our experience, treatment-related deaths The case is there."

Even with these sober warnings in mind, there is nothing wrong with the growing optimism of cancer researchers. They began to understand when the brakes would stop the body's immune response, when it was necessary to step on the accelerator to get the reaction into the high gear, and when it was safe to do both. As researchers combine different treatments and drug doses, they can see improvements in response rates and better treatments for the most serious side effects.

Hot and cold tumor
Researchers have developed a number of different methods to adjust a patient's immune system to more effectively identify and attack harmful tumors. Some treatments use so-called monoclonal antibodies that interfere with cancer cells to deceive the immune system, ignoring their ability. These therapies, known as checkpoint suppression, currently appear to be most suitable for lung cancer caused by melanoma and smoking.

This does have a credible biological cause. Lung cancer in both melanoma and smokers is caused by environmental exposure, the former being ultraviolet light in the sun and the latter being a carcinogen in tobacco smoke. Therefore, a large number of mutations occur in the DNA in the damaged cells. These mutations in turn lead to the production of many abnormal proteins, which are often recognized as potentially dangerous by the immune system, and any cells containing these proteins are quickly labeled and destroyed.

Researchers refer to these malignancies as "hot" tumors because they produce many abnormal proteins that the immune system may notice. Such tumors take a long time to find ways to evade the immune system, which is one of the reasons why melanoma and lung cancer usually take decades to become large enough to threaten the lives of patients.

In these cases, the immune system has sent a large number of immune cells to the tumor, but no matter when they arrive, the cancer cells can always manage to cope with the past. Checkpoint suppression wakes up immune cells that have entered the tumor and begins to kill malignant cells found nearby and in other parts of the body.

Interestingly, the combination of checkpoint suppression drugs in patients with melanoma caused extreme side effects that were weaker than those in lung cancer patients. “This is something that has only recently been realized, about the past two years,” said oncologist Jedd Wolchok of the Sloan-Kettering Memorial Cancer Center in New York. “The same drug, the same dose, patients with different cancers. It may have different tolerances. For patients with lung cancer we may have to use small doses of the drug. (Immunotherapy) is not a one-size-fits-all approach."

In any case, many types of cancer (such as prostate cancer, ovarian cancer, and pancreatic cancer) are caused only by a few genetic mutations. They do not produce a large number of defective proteins, which cause the immune system to respond. Therefore, these tumors are usually not filled with a large number of immune cells that are dormant and are waiting to be reawakened; so checkpoint suppression generally does not work for them. In the words of cancer immunologists, they are "cold" tumors.

However, at this meeting some researchers introduced studies to convert this cold tumor into a hot tumor so that they could then use immunotherapy to deal with these tumors. For example, Padmanee Sharma, an immunologist at the University of Texas Anderson Cancer Center, described a study in which a male patient with malignant prostate cancer was treated with hormones before surgery to kill a portion of the cancer cells before tumor removal. Once these cells die, various proteins and other compounds inside them are released into the body. In this way, it is much easier to get the immune system to focus on these cells and transport the immune cells to remove trace tumors that remain in the body after surgery. Unfortunately, Sharma told the audience that the subsequent response to the booster drugs used by them was short-lived. However, she and her colleagues are looking for different ways to extend the efficacy.

Find the right balance
In fact, the idea that the immune system can be acted upon without having to kill all the cancer cells has sparked interest among many people at the conference. Ira Mellman, vice president of tumor immunology company Genentech, asked aloud, "Is chemotherapy possible to some extent immunotherapy?" By killing some cells, the immune system responds better in later treatment. In some cases, the release of oncoprotein initiates an immune response. In other cases, chemotherapeutic drugs, such as gemcitabine, actually loosen the brakes of the immune system by temporarily removing cells that normally function to suppress the immune system.

Ron Levy, an oncologist at Stanford University, introduced his own research. He killed some malignant cells in low-dose radiation therapy in 15 patients with non-Hodgkin's lymphoma, with some visible tumors. He then injected the experimental immunostimulatory compound directly into a single lesion in each patient. In this way, the amount of drug required to trigger the reaction can be reduced. The effect on a single tumor is sufficient to trigger a systemic immune response, with less dose than for all tumors.

Most patients in Levy's study showed some response; in some people, even untreated tumors began to shrink. In general, it takes half a year to two years to see such changes. A 38-year-old male patient had a complete disappearance of the tumor (all observable cancer characteristics of the entire body disappeared), and this result lasted for more than a year. ("The complete disappearance of the tumor" does not necessarily equate to a cure, as some of the undetected tumors may still lurk somewhere in the body.) "We are working hard to make this response more common and longer lasting," Levy said. His next step is to try to combine this method of stimulating the immune system with a monoclonal antibody (usually 1/20 of the dose) that prevents the tumor from shutting down the immune system. "We hope to eliminate toxicity by topical administration and lowering the effective dose," he told attendees. Although Levy has begun to treat some people with this new combination, he is not ready to share the results.

The researchers also proposed several other promising immunotherapies at the meeting, but these comprehensive discussions are inseparable from the so-called CAR T cells, many of which have been approved by the FDA for the past 18 months. Treating a rare disease or identifying it as a “breakthrough status” (a special approval channel can be taken).

CAR T cells are genetically engineered immune cells that attack tumors in a more powerful way than normal immune cells. To date, clinical trials at the Sloan-Kettering Cancer Memorial Center, the Fred Hutchinson Cancer Research Center and the University of Pennsylvania School of Medicine have shown that this method has a remission rate of approximately 90% for advanced cancers in some blood and lymphatic systems. (Re-emphasizing that this is not the same as healing, but it is still shocking).

"There are at least 300 known cancers, each with different characteristics," said Carl June of the University of Pennsylvania. However, he added, "I think we have enough tools to draw a solution roadmap, so stay tuned."

Source: Author Kristen Gorman

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