Immunotherapy: Revolutionary Cancer Treatment
Over the years, the treatment of cancer has diversified exponentially; however, despite the progress made in cancer drug research (and treatment), the number of cancer deaths are predicted to double by 2030.
Immunotherapy is rapidly gaining momentum as an effective treatment approach in numerous types of cancer. Harnessing the body’s immune system to fight cancer, immunotherapy is effective in that it can selectively target specific mechanisms of cancer cells. Immunotherapy - a unique approach to fight cancer by boosting the natural defenses of the immune system, either passively or actively. Passive immunotherapy involves providing the immune system with components (usually produced outside the body) required to initiate an immune response, such as antibodies. Active immunotherapy involves initiating a direct immune response to fight the disease.
The immune system defends the body against disease, infection and foreign substances. The immune system is composed of several different types of white blood cells each carrying out a specific function, lymphocytes (B and T cells, natural killer cells) provide protection against cancer, other diseases and infection. In addition, the immune system can “detect” non-self-substances within the body, and deliver an immune response by producing antibodies that target foreign material (antigens). Other white blood cells secrete cytokines when an antigen is present; cytokines are regulatory chemicals in terms of immunity and inflammation.
The challenge of destroying cancer cells
Cancer cells have the capability of evading the immune system through several mechanisms, this may include minimizing tumor antigen expression on their surface and escaping detection by the immune system, express proteins that inactivate immune cells or induce cells in the surrounding area to release chemicals that suppress the immune response. By evading the immune system, cancer cells are able to proliferate and survive, thereby spreading to other parts of the body (metastases).
Immunotherapy is designated to overcome these mechanisms and deliver a powerful response against tumors, through counteraction of cancer signals or boosting an immune response. Depending on the type of immunotherapy, patients may experience varied side effects from flu-like symptoms to a loss of appetite; your oncologists will discuss the possible side effects prior to commencing treatment.
Immunotherapy US versus Israel
Treatment approaches in the US are currently more focused on conventional cancer treatments such as chemotherapy, radiation therapy and surgery; immunotherapy is the lesser used form of treatment. However, there is a rapidly growing interest in the benefits and use of immunotherapy, extending from offering a preventive vaccine (cervical cancer) to prolonging the life of a patient (metastatic melanoma). The field of immunology holds potential in treating nearly every cancer type, however, due to strict regulations in the US it may be harder for patients (particularly cancer patients) to receive immunotherapy treatment, despite FDA approval.
Israel is the top choice in cancer treatment: Patients can expect tailored treatments by world-renowned oncologists using the latest diagnostic technologies and treatment approaches. Patients receive medical treatment at the fraction of the cost compared to what they would pay in the US. Israeli specialists have trained in international institutions including the US; many continue to further their qualifications making them the top in their respective field. Medical tourists that come to Israel from the US (for example) are not bound by the bureaucracy of receiving immunotherapy drugs; under the recommendations of highly qualified specialists in Israel, if indicated, a patient has further options of receiving treatment with immunotherapy, particularly in cases of advanced stage cancer (metastatic cancer) that has not responded to preceding treatments.
The main types of immunotherapy include cancer vaccines, monoclonal antibodies or non-specific immunotherapies (cytokines):
Since the inception of cancer treatment using monoclonal antibodies (mAbs) in 1981, there has been huge progress in this approach for the treatment of cancer. Lab-synthesized components of the immune system (antibodies) that are designed to target specific areas of cancer cells, either by preventing cancer cells from evading immune cells, block growth signals, stop angiogenesis (the formation of new blood vessels), or used as deliver vessels for chemotherapy (or radiation) drugs to cancer cells.
Decades of cancer research prompted different types of cancer vaccines which due to the complexity of the immune system and the cancer cells ability to elude the immune system, has proved challenging. Scientists thus couple vaccines with adjuvants that increase the immune’s response. Patients with advanced, recurrent prostate cancer that also no longer responds to hormone therapy, are given Provenge (sipuleucel-T) a dendritic cell vaccine, which uses the patient’s own immune cells (genetically modified in the lab) to induce an immune response when injected back into the patient. Provenge, FDA-approved has shown great promise in prolonging the lives of men with prostate cancer than other treatments.
Oncolytic viruses are lab modifications and manipulation of viruses that infect and kill cancer cells; in addition, oncolytic viruses boost the immune’s response. FDA-approved Imlygic (talimogene laherparepvec) is an example: It boosts the production of a protein GM-CSF to treat inoperable melanoma tumors in the skin or lymph nodes. This injectable treatment has been able to shrink some of these tumors.
Immune checkpoint inhibitors
Immune checkpoint inhibitors - A promising type of immunotherapy, in which treatment works on the molecules that act as checks and regulators of immune responses, by blocking or stimulating an immune response to unleash or boost an anti-cancer immune response.
Tumor cells have the ability of preventing their destruction by manipulating the signal of immune cells (“checkpoints”). Ipilimumab (Yervoy) a monoclonal antibody, which attaches to the checkpoint protein CTLA-4 (on T-cells) in the treatment of melanoma. The drug causes T-cells to stay switched on in order to attack tumor cells, working for a fifth of patients. When ipilimumab is combined with another drug nivolumab (yet to be licensed), results indicate a 58% reduction in tumor size – published in the New England Journal of Medicine. This method of combining immunotherapy treatments may prove effective with other cancer types, but in order to prevent severe side effects, identifying the patients that will respond well to treatment is crucial. In 2012, the UK’s National Institute for Health and Care Excellence (NICE) approved ipilimumab. Leading oncologist Professor Nir Peled at Herzliya Medical Center a private hospital in Israel, adds, “We can already count 16 “immune checkpoint” drugs in the pipelines of pharmaceutical companies around the world, in various stages of testing. Almost all the drugs are first tested on melanoma patients; however, it seems that they will be suitable for other types of cancer as well”. He further emphasized the benefit of checkpoint inhibitor drugs, “We see already today, in the experimental treatments that are being carried out in our center, significant lengthening of life. People we thought would survive for two months are surviving for more than a year.”
Other immunotherapy approaches
Currently numerous clinical trials are taking place for a revolutionary type of cancer treatment using self-immune cells. Chimeric antigen receptor (CAR) T-cell therapy, a new and promising type of immunotherapy, utilizing monoclonal antibodies and the cytotoxicity of T-cells that target tumor cells by recognizing specific antigens. This involves extracting blood to retrieve T-cells from the patient that are then genetically altered in a lab by the addition of CARs on their surface. Once these newly modified cells multiply they are infused back into the patient’s blood and destruct tumor cells. Patients with blood-cancer like leukemia and lymphoma, who in the past had an unsuccessful treatment with over 10 drugs, were found to have remarkable results when CAR is applied – including tumor shrinkage over a few years.
Other revolutionary immunotherapy treatments like TIL (tumor infiltrating lymphocytes), has given patients with a poor prognosis a new lease of life, take for example the CEO of a huge mall in Israel, Shmuel Bin had advanced cancer (metastasis). Following his first round of gruesome chemotherapy, he was told if that if he did not do another round he would have only 4-8 months left to live. He complied and had another round of chemo and interleukin, followed by TIL treatment in Israel. After doctors surgically removed metastasis from his lung, he had to undergo a round of chemotherapy prior to TIL; the results outweigh the negative aspects – his tumor shrunk after his first CT scan. Today most of the metastases disappeared or shrunk and he is living 5 years later. Other lung cancer immunotherapy drugs include:
Recently FDA approved drug Keytruda (pembrolizumab) in conjunction with a diagnostic test detects a protein PD-L1 in metastatic non-small cell lung cancer (NSCLC). This drug is an immune checkpoint inhibitor - it blocks a specific pathway that inhibits T-cells from attacking cancer cells.
Furthermore, Keytruda can be used in the treatment of inoperable melanomas, as well as disease progression after ipilimumab, and for those with a BRAF V600 mutation. In other developments, pharmaceutical giant Pfizer’s merging with Merck KGaA in November 2014, a deal potentially worth over $2.8 billion, will see them jointly develop avelumab (monoclonal antibody) for multiple cancer types. Most recently, the joint pharmaceutical companies were granted a fast-track designation (to expedite the clinical trial process) of the drug for a rare and aggressive skin cancer, Merkel cell carcinoma. Avelumab has demonstrated positive results in other cancers like NSCLC and recurrent ovarian cancer.
The FDA approved two drugs for colon cancer in 2014, Erbitux (cetuximab) a monoclonal antibody to treat metastatic colon cancer and Avastin (bevacizumab) to suppress angiogenesis of tumors. Furthermore, Vectibix (panitumumab) was FDA approved in 2007. Unfortunately, panitumumab and cetuximab are ineffective in patients that carry a gene mutation known as K-ras.
It is estimated that around 1 in 8 American women will develop invasive breast cancer – for men it is 1 in 1,000. On a global scale, in 2012, there were over 1.68 million new diagnoses and 520,000 mortalities due to breast cancer. Despite the progression in delivering HER2-directed therapies with optimized efficacy, some patients may relapse, while those with triple negative breast cancer respond less effectively to a targeted treatment approach. Prognoses depend on newer, more advanced therapeutic regimes; immunotherapy has fewer side effects compared to conventional breast cancer treatment. Currently many cancer vaccines, checkpoint inhibitors, monoclonal antibodies and more are being investigated.
Bacillus Calmette-Guérin (BCG) is a weakened live strain of the Mycobacterium bovis and the vaccine for tuberculosis; it is FDA-approved and the primary treatment for bladder cancer and reduces the risk of recurrence. It is generally not used in the US due to fears of infection by the bacterium. What makes this treatment stand out is its high effectiveness (70%) if the tumor is considerably small, i.e. non-invasive or early-stage tumor or carcinoma in situ (CIS).
New generation of cancer therapy
Continual advancements in the field of immunotherapy to further understand why some patients have a better response rate than others, finding further possible immunotherapies for all cancer types, as well as improving the efficacy of existing immunotherapies (by combining them with other cancer treatments like chemotherapy) may all lead to a new generation of cancer treatment. While in so doing, designing immunotherapy with minimal side effects and one that will have a long-lasting effect for patients.