Chimeric antigen receptor-T cells targeting epithelial cell adhesion molecule antigens are effective in the treatment of colorectal cancer.

OBJECTIVE: To construct chimeric antigen receptor (CAR)-T cells targeting epithelial cell adhesion molecule (EpCAM) antigen (anti-EpCAM-CAR-T). METHODS: A third-generation CAR-T cell construct used a single-chain variable fragment derived from monoclonal antibody against human EpCAM. Peripheral blood mononuclear cells were extracted from volunteers. The proportion of cluster of differentiation 8 positive (CD8+) and CD4 + T cells was measured using flow cytometry. Western blot was used to detect the expression of EpCAM-CAR. The killing efficiency was detected using the MTT assay and transwell assay, and the secretion of killer cytokines tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was detected using the ELISA. The inhibitory effect of EpCAM-CAR-T on colorectal cancer in vivo was detected using xenografts. RESULTS: It was found that T cells expanded greatly, and the proportion of CD3+, CD8 + and CD4 + T cells was more than 60%. Furthermore, EpCAM-CAR-T cells had a higher tumour inhibition rate in the EpCAM expression positive group than in the negative group (P < 0.05). The secretion of killer cytokines TNF-α and IFN-γ in the EpCAM expression positive cell group was higher than that in the negative group (P < 0.05). In the experimental group treated with EpCAM-CAR-T cells, the survival rate of nude mice was higher (P < 0.05), and the tumour was smaller than that in the blank and control groups (P < 0.05). The secretion of serum killer cytokines TNF-α and IFN-γ in tumour-bearing nude mice in the experimental group treated with EpCAM-CAR-T cells was higher than that in the blank and control groups (P < 0.05). CONCLUSION: This study successfully constructed EpCAM-CAR cells and found that they can target and recognise EpCAM-positive tumour cells, secrete killer cytokines TNF-α and IFN-γ and better inhibit the growth and metastasis of colorectal cancer in vitro and in vivo than unmodified T cells.

DNT Cell-based Immunotherapy: Progress and Applications.

Cancer immunotherapy has firmly established a dominant status in recent years. Adoptive cellular immunotherapy (ACI) is the main branch of immunotherapy. Recently, the immune effector cells of ACI, such as T cells, NK cells, and genetically engineered cells, have been used to achieve significant clinical benefits in the treatment of malignant tumors. However, the clinical applications have limitations, including toxicity, unexpectedly low efficiency, high costs and strict technical requirements. More exploration is needed to optimize ACI for cancer patients. CD3+CD4-CD8- double negative T cells (DNTs) have emerged as functional antitumor effector cells, according to the definition of adoptive immunotherapy. They constitute a kind of T cell subset that mediates nontumor antigen-restricted immunity and has important immune regulatory functions. Preclinical experiments showed that DNTs had a dual effect by killing tumor cells and inhibiting graft-versus-host disease. Notably, DNTs can be acquired from healthy donors and expanded in vitro; thus, allogeneic DNTs may be provided as "off-the-shelf" cellular products that can be readily available for direct clinical application. We review the progress and application of DNTs in immunotherapy. DNTs may provide some novel perspectives on cancer immunotherapy.

[Approach to the road of vigorously developing Chinese medicine by scientific location of channels and collaterals].

Through researches of channels and collaterals and clinical practice of many years, the authors understand that Chinese medicine, which considers the human body as an interrelated, mutual constraints, whole, dynamic living system, has gradually become an important part of modern medicine. Channels and collaterals are a closed loop system which is communicated and linked by energy and information in the form of electromagnetic oscillation, reflecting many characteristics similar to quantum. Channels and collaterals are not a fixed organizational structure. Studies on channel and collaterals find that the track of the propagated sensation along channels (PSC) have the phenomenon drifting about. This exactly reflects the law of channels dynamically running. By information triggering and living resonance, channels and collaterals bring into play entirely regulative action. The innovative treatment of channels and collaterals followed by characteristics and laws of quantum can get a better curative effect. Theory of channels in the position of quantum information medical science provides an important breach for modernization of Chinese medicine.

[Study on theory and clinical application of meridians (III)].

OBJECTIVE: To probe into essence of meridians. METHODS: To examine meridians, acupoints, brain and relative organs by SQUID and fMRI, and to analyze the results. CONCLUSION: A relative stable circular current of electromagnetic and chemical oscillation along the low electric resistance pathway was found. Competition of different frequency oscillation often yield resonance in some positions of the human body so as to form "oscillatory network" and "strange point" with the electromagnetic and chemical oscillation circulating dominant position in the body, which is possibly meridians and acupoints with regulative actions. The brain is the center of meridians. In different physiological or pathological process, characteristic changes and negatively correlative phenomenon of electromagnetic spectrum at acupoints and the brain are possibly key mechanisms in dynamic regulation of meridians.

[Relationship of meridians with human material and energy systems study on theory and clinical application of meridians (IV)].

OBJECTIVE: To expound the relationship between meridians and the human two information systems, material system and energy system. METHODS: Summarize and analyze the results of experimental and other studies. CONCLUSION: The carrier of the meridian is human material system. The nerve, body fluid, microcirculation and chemical factors take part in meridian circulation, and it must depend on the energy information system which works mainly at the form of electromagnetic and chemical oscillation with functions of physiological regulation and pathological repair. Oscillation parameters include various signals of regulating development and physiologic activities, and coordinate functions of organs and tissues. The meridians have the "quantum" characteristics, material particles coexist and exchange each other with electromagnetic and chemical oscillation characteristic.

[Meridian regulation is a course of communicating and implicating of the informational system with the material system].

OBJECTIVE: To approach to the intrinsic mechanism of meridian regulation. METHODS: Summarize and analyze the results of the author's studies and the development of other studies about life regulating and meridian at home and abroad. CONCLUSION: The regulating mechanism of meridians has two levels. The macroscopic regulation center is the brain, and the microscopic regulation base is the energy and informational current that depends on electromagnetic and chemical oscillation mainly. The meridian regulation is the process of the energy and informational system communicating and implicating with the material system. Neuroendocrine is the link of communicating and implicating, and Ca2+ oscillation frequencies exert intermediary function between the two systems.