The American Cancer Society estimated that in 2015, there were 1,658,370 new cases of cancer diagnosed in this country and some 589,430 deaths. These widespread numbers mean that whether a new doctor enters into general practice, oncology or some other specialty, they are likely to have to work with cancer patients. Because of this, a good understanding of new developments in cancer treatment is important in order to inform and educate patients fully about their potential options.
One of the most promising lines of cancer treatment is that of immunotherapy. This article covers several of the most-researched forms of this kind of therapy in order to familiarize doctors with the new techniques being used to help patients battle their cancer.
Immunotherapy Defined
Immunotherapy is defined as a treatment option which harnesses the abilities of the body’s own immune system in order to recognize and attack cancer cells. This is not as simple as it sounds. It can be difficult for the immune system to do on its own for several reasons: the system does not recognize cancer cells as “foreign” and won’t attack them, or it is not strong enough to mount an adequate defense, or the cancer cells emit chemical compounds which act as a “check” on the immune system response. The goal of immunotherapy is to overcome these possible barriers and help the body’s own system fight this difficult and complex disease.
Why Immunotherapy Research is Important
Researchers writing in the Yale Journal of Biology and Medicine note that simply by virtue of the number of deaths that cancer causes—approximately 1 in 4 of the total annual deaths in America—that the need for novel and effective therapies is intensive. They go on to note that “although surgery, radiation therapy and chemotherapy have been significantly improved over the past years, metastatic disease can rarely be controlled by these treatments and cure remain scarce,” but then remark that “immunotherapy…may become a powerful new weapon in the arsenal of treatments that oncologists can offer their patients”.
The authors back this statement up by noting the many advantages that immunotherapy can have over the more traditional treatments they have mentioned, including:
● The ability of activated immune cells to recognize and target remote areas of cancer cells that traditional surgery cannot access
● The fact that stimulated immune system cells will not necessarily target only cells that rapidly divide in the way that chemotherapy or radiation therapy do; this makes it a better therapy for cancer stem cells and for cancer cells which have slower rates of reproduction.
● The ability of these stimulated cells to target cancerous growths and tissues more specifically while leaving healthy surrounding tissue intact and healthy; this can still be a challenge with more traditional treatments.
● The presence of memory cells which can prevent cancer from returning after its initial treatment.
● The power of immune cells to target more microscopic and remote areas of cancerous presence than is possible with current treatments.
Because of the number of new diagnoses and deaths from cancer annually, delving more deeply into the therapeutic potential of immunotherapy is incredibly important. It offers a more targeted form of therapy and, in some cases, avoids the side effects which can seriously impact the quality of life for cancer survivors.
Different Types of Immunotherapies
Monoclonal antibodies. Monoclonal antibodies are proteins made from the immune system. They are important because researchers have been able to manipulate in the laboratory and redesign them genetically in order to recognize and attack a specific type of cancer cell. This kind of targeted therapy can help overcome one of the most challenging aspects of cancer treatment: finding ways to destroy malignant cells without doing damage to healthy surrounding tissues.
Therapies based upon the use of antibodies are some of the most widely researched—and commercially successful—forms of immunotherapy for cancer: there are now 13 different monoclonal antibodies (mAB’s) currently available in Europe and North America. And three of them, including bevacizumab, rituximab and trastuzumab, are actually top sellers. However, authors of a study on these medications, published in the journal of the Hematology-Oncology Clinics of North America, acknowledge that there are still challenges to be overcome in order to improve these therapies, including problems with a buildup of resistance in the patient, the ability to access the targets of the therapy and the reaction of the mAB to the complexities of the bodily system and the disease process.
Immune checkpoint inhibitors. Cancer cells have the ability to sometimes put a “check” on the body’s natural immune response; treatments in this category help to remove this check so that the system is able to recognize cancer cells as foreign bodies and successfully attack them.
One particular type of cancer which has proven susceptible to this kind of therapy is urothelial bladder cancer (UBC), which researchers writing this year in the journal Clinical Cancer Research note is, globally, one of the most widespread forms of cancer—and one with a poor prognosis for patients. The standard treatment for UBC remains platinum-based chemotherapy, which does not appear to have a marked effect upon patient outcomes. This is why they note that experiments with immune checkpoint blockades appear to be having more preliminary success in treating this very serious form of cancer.
Cancer vaccines. Vaccines are substances injected into the human body in order to stimulate an immune response and help the body to recognize and kill off cancer cells.
Scientists, writing last winter in the National Review of Clinical Oncology note that strong clinical evidence supports the use of cancer vaccines for therapeutic use due to their potential to elicit host-specific and tumor-specific immune responses from the systems of cancer patients. Vaccines and similar active immunotherapies are use to induce or to strengthen the body’s immune responses against the presence of cancer cells. Authors note, however, that eliciting this response is a complicated, multi-faceted task and requires the right combination of antigens and adjuvants—delivered by the right vehicle by the right route—in order for them to be effective.
Oncolytic viruses. As the name implies, these viruses are able to infect and kill cells, and researchers have found that they can be genetically manipulated in the lab and injected into patients so that there are able to target and lyse cancer cells. One example of this is the Imlygic virus, which has been modified to help strengthen immune response and has been injected on a bi-weekly basis to help treat melanoma of the skin and lymph system.
Another important example of the use of oncolytic viruses for the treatment of cancer is a recent study which noted that the limited efficacy of treatment for pancreatic cancer has resulted in poor prognosis and poor patient quality of life in those with this diagnosis—and made it more important than ever that alternative treatment modalities be found. One such potential treatment is the use of oncolytic viruses, which are valued for their ability to activate the immune system against cancer cells. In particular, this study looked at three specific characteristics—transgene expression, toxicity and the antitumor effect—of the adenovirus and the Newcastle Disease virus and found that moderate doses of the adenovirus, followed in a week by doses of the Newcastle Disease virus stimulated the immune system against pancreatic cancer cells and showed marked antitumor effect.
Chimeric antigen receptor (CAR) T-cell therapy. Scientists have discovered immune system cells deep inside the tissues of some tumors. These special cells have been labelled tumor-infiltrating lymphocytes which researchers have managed to remove from the tumors, manipulate in the lab, and reinject into the patient to help kill off cancer cells.
Chimeric antigen receptor-engineered T-lymphocytes were the subject of research published just this year, which looked at how this engineering could help in the treatment of lung squamous cell carcinoma (LSCC). The researchers found that these modified cells, when reinjected into the patient, were able to lyse cancer cells and successfully inhibit tumor growth. They also noted that these T-lymphs were able to persist in vivo and to efficient infiltrate and destroy malignant cells. Scientists working on this project noted that “Taken together, these findings indicate that CARgpc3 T cells might be a novel potential therapeutic agent for the treatment of patients with lung squamous cell carcinoma”.
In conclusion, there are a variety of immunotherapy techniques that scientists are working to better utilize in order to recruit the body’s own response system in the fight against the presence of cancer cells. These novel techniques often have fewer or less devastating side effects than traditional therapies, and also appear to often be linked with improvement in overall patient outcomes, particularly for conditions such as pancreatic cancer and urothelial bladder cancer, which generally have not proven to be responsive to traditional, more mainstream treatments. Doctors familiar with these new therapies, and their strengths and weaknesses, can help educate their patients on their full range of treatment options so that the the patients, in turn, can make an informed decision about battling this disease. .
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Brian Wu, MD, Ph.D., MNM, graduated from the University of Maryland with a Bachelor’s of Science in Physiology and Neurobiology, and graduated from the Keck School of Medicine (University of Southern California) with an MD with a focus on holistic care and treatment. He currently holds a Ph.D. in integrative biology and disease for his research in exercise physiology and rehabilitation.