Chimeric antigen receptor-modified immune cells and their application in tumor immunotherapy / 中国肿瘤生物治疗杂志

@# [Abstract] Chimeric antigen receptor-modified T cells (CAR-T cells) refers to the products after transferring genetic material with specific antigen recognition domain and T cell activation signal domains into T cells by gene modification technology, thus rendering the modified T cells activated by binding directly to specific antigens on the surface of tumor cells in the CAR-T cell therapy. In recent years, CAR-T cells have achieved remarkable results in the treatment of hematological diseases, bringing new hope to patients with hematological tumors. CAR-T cell therapy has become one of the most promising tumor immunotherapies, and CAR-T cells have become a hot spot for research and development by major companies. However, due to the side effects such as cytokine storm and poor treatment effect on solid tumors, the clinical application of CAR-T cells still faces challenges. In addition to traditional T cells, other immune cells are being explored for the application of CAR, for example, modifying immune cells such as NK cells, γδT cells, NKT cells, and macrophages to improve the effectiveness of these immune cells in killing tumors, and simultaneously reduce the adverse reactions caused by CAR-T cell immunotherapy. This review compares the advantages and disadvantages of different CAR-modified immune cells in tumor therapy and provides new ideas and enlightenments for the clinical development and application of CAR-modified immune cells in tumor immunotherapy.

Detection and clinical significance of NKG2D of CD+8 NKT cell and its ligand sMICA from peripheral blood in patients with esophageal or cardiac carcinoma / 肿瘤研究与临床

Objective To evaluate the clinical diagnostic application and operative efficacy of the expression of NKG2D in peripheral blood CD+8 NKT cell and its ligand sMICA in patients with esophageal or cardiac carcinoma.Methods The peripheral blood NKG2D positive CD+8 NKT cell percentage was concomitantly determined by flow cytometry in 53 preoperative patients including 29 postoperative patients with esophageal or cardiac carcinoma and 30 healthy controls.The serum sMICA was determined by ELISA.Results The peripheral blood NKG2D positive CD+8 NKT cell percentage in patients was significantly lower than that in controls [(77.632±8.972) % vs (89.053±6.515) %] (t = -6.113,P ＜0.05); with stage Ⅱ,Ⅲ,Ⅳ,it decreased significantly in order (F = 99.251,P ＜0.01);with lymph node metastasis lower than that without lymph node metastasis (t = -10.384,P ＜0.01); squamous carcinoma was higher than adenocarcinoma (t =9.899,P ＜0.01); postoperative was significantly higher than preoperative (t =-4.319,P ＜0.01).The level of serum sMICA in patients was significantly higher than that in controls [(326.28±85.407) pg/ml vs (210.00±92.560) pg/ml](t =7.292,P ＜0.01); with stage Ⅱ,Ⅲ,Ⅳ,it increased significautly in order (F =63.355,P ＜0.01); with lymph node metastasis higher than that without lymph node metastasis (t =7.770,P ＜0.01); squamous carcinoma was lower than adenocarcinoma (t =-7.593,P＜0.01); postoperative was significantly lower than preoperative (t =7.027,P ＜0.01).Serum sMICA could inhibit peripheral blood CD+8 NKT cell activation receptor NKG2D (F =142.773,P ＜0.05),determination coefficient R2 = 0.7368.Conclusion The level of peripheral blood CD+8NKT cell activation receptor NKG2D and serum sMICA in patients could be an assistant indicator for

Natural killer T cell and pathophysiology of asthma / 소아과

Natural killer T (NKT) cell is a special type of T lymphocytes that has both receptor of natural killer (NK) cell (NK1.1, CD161c) and T cell (TCR) and express a conserved or invariant T cell receptor called Valpha14Jalpha18 in mice or Va24 in humans. Invariant NKT (iNKT) cell recognizes lipid antigen presented by CD1d molecules. Marine-sponge-derived glycolipid, alpha-galactosylceremide (alpha-GalCer), binds CD1d at the cell surface of antigen-presenting cells and is presented to iNKT cells. Within hours, iNKT cells become activated and start to secrete Interleukin-4 and interferon-gamma. NKT cell prevents autoimmune diseases, such as type 1 diabetes, experimental allergic encephalomyelitis, systemic lupus erythematous, inflammatory colitis, and Graves' thyroiditis, by activation with alpha-GalCer. In addition, NKT cell is associated with infectious diseases by mycobacteria, leshmania, and virus. Moreover NKT cell is associated with asthma, especially CD4+ iNKT cells. In this review, I will discuss the characteristics of NKT cell and the association with inflammatory diseases, especially asthma.

The study of changes on NKT cells of experimental autoimmune encephalomyelitis (EAE) mice / 细胞与分子免疫学杂志

AIM: To observe the changes of the number of NKT cells in spleens and livers of induced model of experimental autoimmune encephalomyelitis (EAE), and to study the role NKT cells play in the immunoregulation of EAE. METHODS: C57BL/6 mice were immunized with MOG peptide and received clinical evaluation daily. The mice were sacrificed at the fastigium and the splenic and hepatic lymphocytes were isolated. The changes of NKT cells in normal and EAE C57BL/6 mice were detected by flow cytometry. RESULTS: The percent of NKT cells in lymphocytes of different organs of EAE model were greater decreased than in that of normal mice. The percent of NKT cells in splenic lymphocytes of normal mice was 2.22± 0.14, while that in EAE mice was 1.94±0.07 (P < 0.05). The percent of NKI cells in hepatic lymphocytes of normal mice was 5.52±2.17, while that in EAE mice was 2.67± 1.41 (P < 0.05). CONCLUSION: The proliferation of splenic and hepatic NKT cells in C57BL/6 mice are inhibited in EAE model, which may indicate that the immune function conducted by NKT cell is down regulated in EAE mice.