Types of immunotherapy
Depending on the specific type of immunotherapy involved, it can either kick-start the immune system’s response to cancer, enhance immune system activities that are already active, or suppress the immune system in part or whole to allow other cancer treatments to work.
Each type of immunotherapy represents an entire class of therapeutic strategies targeting the immune system, which can be classified as either nonspecific or specific immunotherapies. Nonspecific immunotherapies induce a general immune response whereas specific therapies induce a particular immune response to a specific antigen.
In passive immunotherapy, patients can be injected with man-made immune system proteins that the body may be lacking to enhance immune system performance. This process stimulates a temporary anti-tumor effect, enhancing pre-existing immune responses of combating infection. Given the short-lived anti-tumor effect, the duration of passive immunotherapy treatment protection is short-term and chronic administration may be needed.
In active immunotherapy, patients can be given drugs in the form of a cancer vaccine or through cellular immunotherapy to activate their immune system to induce its own response. After analyzing tumor cells and recognizing antigens, a treatment drug is created to generate a tumor-specific immune response that is long-lasting or in constant protective defense, even after treatment has stopped.
Immunotherapy for malignant mesothelioma and gastric cancers
Gastric cancers are responsible for the second most cancer-related deaths worldwide. Although medical and surgical treatments have improved for gastric cancers, survival rates remain poor for both lung and gastric cancer patients.
Currently, approaches for immunotherapy in gastric cancer rely on the use of immunocytes, white blood cells that produce antibodies or trigger an immune response. Specifically, the current immunotherapy is designed to activate tumor specific cytotoxic T cells or to specifically bind target molecules or proteins expressed on the malignant tumor cells. In their research, a number of tumor rejection antigens have also been identified.
Experimental vaccination strategies are also in trial, including use of whole protein and peptide vaccines based on identification of peptides recognized by cytotoxic T lymphocytes and helper T lymphocytes. Tumor rejection antigens are selectively expressed in human tumors including gastric cancer, which can be recognized by cytotoxic T cells.
Trials for checkpoint blockade with the aggressive cancer, mesothelioma are ongoing as well. Including therapies such as nivolumab, pembrolizumab (Keytruda), tremelimumab (monoclonal antibody), avelumab and durvalumab mostly in the pretreated setting.
Though malignant mesothelioma is rare, it is a deadly malignancy and lead to the deaths of 2,597 people in the U.S. in 2015 alone. The Centers for Disease Control and Prevention reported additional malignant mesothelioma mortality rates and demographics in March of 2017, of which 80% of patients have clear asbestos exposure as the etiology. Immunotherapy shows early but promising results for malignant mesothelioma.
A recent study evaluating 170 samples malignant pleural mesothelioma samples with IHC, ISH and next generation and sanger sequencing demonstrated that a significant fraction of tumors were positive for PD-1 and PD-L1 expression – a checkpoint signal that dampens T cells activation to allow tumors to escape the adaptive immune response.
Although immunotherapy treatments are limited to clinical trials for mesothelioma patients, researchers have seen promising results from these studies. One positive example is mesothelioma patient Mavis Nye, who was out of treatment options and on her deathbed before she was accepted into a clinical trial testing of Keytruda (pembrolizumab). This passive immunotherapy treatment is known as a targeted therapy checkpoint inhibitor designed to block certain cell interactions, to ultimately help kill cancer cells. To date, this drug has been approved to treat non-small cell lung cancer and melanoma and has even shown some success in treating mesothelioma.
CRS-207, a cancer vaccine that consists of engineered live bacterium, is another exciting form of immunotherapy. It has been coined the “next phase” and is expected to begin recruiting patients later this year. Aduro Biotech, the manufacturer of CRS-207, announced earlier this month that they will be moving forward with a clinical collaboration with Merck, the pharmaceutical company that develops Keytruda. Phase II of this clinical trial will test the effectiveness of CRS-207 with Keytruda on malignant pleural mesothelioma patients whose disease progressed following previous treatment. These two companies are also testing this combination for gastric cancers in another clinical trial.
Immunotherapy theories and treatments have seen major advancements throughout the past 20 years, yet hurdles remain to be overcome before cancer immunotherapy becomes the first line and most reliable and effective cancer treatment. Clinical trials remain promising, however for gastric cancer, lung cancer mesothelioma and more. Follow the Cancer Research Institute’s Cancer Immunotherapy Month website for more information on clinical trials, patient stories and to get involved follow their Facebook Page.