Медицинская иммунология (May 2021)
Development of approaches for cellular immunotherapy of cancer patients
Abstract
To treat the patients with oncological diseases, cellular immunotherapy have been actively developed in recent years. Usage of antitumor adoptive immunotherapy (AIT) based on in vitro activated lymphocytes and natural killer cells (NK cells) is the most urgent issue. Their antitumor potential is enhanced by in vitro cultivation in the presence of cytokines. In vitro incubation of autologous peripheral blood mononuclear cells supplemented with cytokines produces cytokine-induced killer cells (CIK). These cells represent the important component of antitumor protection which may be potentially used for AIT. Currently, the studies in the field of antitumor AIT continues, searching for high-tech and safe methods of cellular immunotherapy in oncology. The article describes results of in vitro activation of lymphocytes from cancer patients (n = 19) in the culture media containing IL-2, IL-12 and IL-15. The ELISA assays revealed differences in the cytokine secretion (IL-2, IL-4, IL-6, IL-10, IFNα, IFNγ, TNFα) after in vitro activation of lymphocytes. It was shown that, for earlier in vitro activation of cells, IL-15 should be supplemented. We also studied the ability of whole blood cells from cancer patients (n = 20) receiving cell immunotherapy vs those non-treated with AIT, as well as healthy donors (n = 10), to secrete cytokines in spontaneous and mitogen-induced cultures. Peripheral blood cells of cancer patients receiving AIT for a year or more proved to show a more pronounced ability to respond to mitogen stimulation, in contrast to the patients who have never received AIT, as well as in relation to a group of donors whose immune system has not been stimulated either. Most likely, this may be explained by the fact, that the in vitro activated CIKs if introduced into the patient’s body, trigger a number of cascadelike intercellular interactions leading to activation of the patient’s immune system cells, especially, antitumor immunity, proliferation of cytotoxic lymphocytes and NK cells, like as in vivo inhibition of immunosuppression. The developed method of CIK production may be offered for carrying out cellular AIT in oncological patients as a novel approach to in vivo activation of the patient’s immune system.
