Immunotherapy is a form of biological therapy that uses the immune system to fight cancer. The body’s immune system recognizes and kills abnormal cells in the body, and has the function of “eliminating foreigners”. However, tumor cells often disguise as “their own” to avoid monitoring by the immune system, and then multiply in the body freely. The main goal of immunotherapy is to improve the immune system’s ability to recognize tumor cells and effectively kill or even eliminate them.
What are the current advances in immunotherapy in the field of gastric cancer? This article will describe the progress of several major immunotherapies.
Gastric cancer vaccine
For gastric cancer, there are a number of vaccine-related studies underway.
The MAGE-3 peptide nanovaccine developed in China inhibited gastric cancer by 37.81% in mice. The combination of vaccines with chemotherapeutic agents is an approach that has received more attention. In a Japanese study, the combination of VEGFR1 (vascular endothelial growth factor receptor 1) and VEGFR2 peptide vaccines with tegeo (S-1) + cisplatin in patients with progressive gastric cancer resulted in a median survival of 14.2 months. G17DT, an “immunogen” with a gastrin profile, theoretically produces antibodies to prevent cell growth in response to gastrin, and has been shown in studies to stimulate an immune response in vivo when combined with 5-fluorouracil + cisplatin, with longer survival in those who develop an immune response.
Immunomodulators
This class of drugs includes nonspecific immune-enhancing drugs and inhibitors that target immune checkpoints.
Non-specific immune-enhancing drugs are, simply, drugs that boost systemic immunity, such as shiitake mushroom polysaccharide (Lentinan), pidotimod, and others.
Immune checkpoint inhibitors, the main function of which is to inhibit tumor cells from sending inhibitory signals to immune cells so that they cannot escape recognition by immune cells. Over the past decade or so, the continued discovery of immune checkpoints has also made them a hot topic of research in oncology treatment, and a large number of drugs have emerged. Currently, the main approved immune checkpoint inhibitors for gastric cancer treatment are the anti-PD-1 (programmed death molecule-1) antibodies pembrolizumab and nivolumab, both of which are listed in the US NCCN gastric cancer guidelines, and both of which are already available in China. In addition, there are ongoing studies of drugs targeting immune checkpoint cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as Tremelimumab (trimethoprim).
Cellular therapy
Also known as cellular percutaneous therapy, it is an emerging therapeutic intervention in which normal immune cells from the patient’s body are extracted, expanded and cultured or modified in vitro, and then infused back into the patient. Some small clinical studies have been conducted only for some advanced patients, which have induced immune responses in some patients and tumor regression in a small number of patients. However, its application has yet to be confirmed by further clinical studies.
In summary, tumor immunotherapy is still in its infancy, with lung cancer and melanoma relatively far ahead of the curve and gastric cancer close behind. The development of immune checkpoint inhibitors is in full swing worldwide, with drugs already on the market, and cellular therapies are slowly maturing and have great potential. Immunotherapy is expected to be a powerful tool for overcoming gastric cancer in the future. (Contributed by Pengliang Wang, Department of Gastrointestinal Oncology, The First Hospital of China Medical University)