- Natural killer cells differentiated in vitro from cord blood CD34(+) cells are more advantageous for use as an immunotherapy than peripheral blood and cord blood natural killer cells. [Journal Article]
- CCytotherapy 2017 Apr 17
- CONCLUSIONS: We are able to generate NK cells from CBCD34(+) cells in high numbers, allowing for multiple infusions of highly cytotoxic NK cells that have potential to further proliferate in vivo, making them a desirable product for application as an immunotherapy in the clinic.
- Chemical and biological properties of a supramolecular complex of tuftsin and cucurbituril. [Journal Article]
- IIInt Immunopharmacol 2017 Apr 17; 47:199-205
- Cucurbituril (CB7) is an uncharged and water-soluble macrocyclic host. CB7 binds to doubly protonated tuftsin, which is the tetrapeptide Thr-Lys-Pro-Arg, with moderate affinity (Ka=2.1×10(3)M(-1))...
Cucurbituril (CB7) is an uncharged and water-soluble macrocyclic host. CB7 binds to doubly protonated tuftsin, which is the tetrapeptide Thr-Lys-Pro-Arg, with moderate affinity (Ka=2.1×10(3)M(-1)). In this study, the host-guest complexation was confirmed by fluorescence titration. This affinity would allow for easy release of the peptide under physiological conditions. According to density functional theory calculations, the structural binding motif involves hydrogen bonding. The most energetically stable form had the Arg side chain inside the CB7 cavity. The effects of the tuftsin-CB7 complex on the proliferation and cytokine activity of immune cells were studied. The complex had broader spectrum immunomodulation than free peptides, and caused statistically significant (p<0,05) changes in cytokine production (tumor necrosis factor-α, interleukin-2, interferon-γ, and interleukin-10) by mononuclear cells. By contrast, the free peptide only activated tumor necrosis factor-α production.
- Ketamine, as adjuvant analgesics for patients with refractory cancer pain, does affect IL-2/IFN-γ expression of T cells in vitro?: A prospective, randomized, double-blind study. [Journal Article]
- MMedicine (Baltimore) 2017; 96(16):e6639
- CONCLUSIONS: In conclusion, we confirmed that just as morphine, ketamine dose-dependently suppressed IL-2 and IFN-γ of activated T lymphocyte of patients with refractory cancer pain in vitro, but the inhibitory action of low dose ketamine could be neglected.
- Gene-modified NK-92MI cells expressing a chimeric CD16-BB-ζ or CD64-BB-ζ receptor exhibit enhanced cancer-killing ability in combination with therapeutic antibody. [Journal Article]
- OOncotarget 2017 Mar 15
- Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. NK-92MI is an interleukin-2 (IL...
Natural killer (NK) cells play a pivotal role in monoclonal antibody-mediated immunotherapy through the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. NK-92MI is an interleukin-2 (IL-2)-independent cell line, which was derived from NK-92 cells with superior cytotoxicity toward a wide range of tumor cells in vitro and in vivo. Nonetheless, the Fc-receptor (CD16) that usually mediates ADCC is absent in NK-92 and NK-92MI cells. To apply NK-92MI cell-based immunotherapy to cancer treatment, we designed and generated two chimeric receptors in NK-92MI cells that can bind the Fc portion of human immunoglobulins. The construct includes the low-affinity Fc receptor CD16 (158F) or the high-affinity Fc receptor CD64, with the addition of the CD8a extracellular domain, CD28 transmembrane domains, two costimulatory domains (CD28 and 4-1BB), and the signaling domain from CD3ζ. The resulting chimeric receptors, termed CD16-BB-ζ and CD64-BB-ζ, were used to generate modified NK-92MI cells expressing the chimeric receptor, which were named NK-92MIhCD16 and NK-92MIhCD64 cells, respectively. We found that NK-92MIhCD16 and NK-92MIhCD64 cells significantly improved cytotoxicity against CD20-positive non-Hodgkin's lymphoma cells in the presence of rituximab. These results suggest that the chimeric receptor-expressing NK-92MI cells may enhance the clinical responses to currently available anticancer monoclonal antibodies.
- Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells. [Journal Article]
- OOncotarget 2017 Mar 18
- The role of IL-2 in HSC maintenance is unknown. Here we show that Il2-/- mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detri...
The role of IL-2 in HSC maintenance is unknown. Here we show that Il2-/- mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2-/- mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2-/- mice shows that the IL-2-Treg cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of Treg activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring Treg population successfully rescued HSC maintenance in Il2-/- mice, preventing IFN-γ activity could do the same even in the absence of Treg cells. Our study suggests that equilibrium in IL-2 and IFN-γ activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-γ treatment might help to restore hematopoiesis.
- Prognostic value of the soluble interleukin-2 receptor level after patients with follicular lymphoma achieve a response to R-CHOP. [Journal Article]
- HHematology 2017 Apr 17; :1-6
- CONCLUSIONS: Among patients with a low pretreatment sIL-2R level who exhibited a positive response to R-CHOP, the posttreatment sIL-2R level may help to identify those with a poor prognosis.
- Evaluation of the role of human β-defensin 3 in modulation of immunity and inflammatory response after knee replacement. [Journal Article]
- ETExp Ther Med 2017; 13(4):1343-1346
- The present study investigated the value of human β-defensin 3 (HBD-3) in adjusting the immunity and inflammatory response of T lymphocytes in the body after knee replacement. Sixty-four cases of kne...
The present study investigated the value of human β-defensin 3 (HBD-3) in adjusting the immunity and inflammatory response of T lymphocytes in the body after knee replacement. Sixty-four cases of knee replacement patients were successively selected and randomly divided into the control group and the observation group each with 32 cases. Once a day, for 7 days, patients in the control group were injected with placebo saline solution in the articular cavity. Levels of Th1 and/Th2, interleukin (IL)-2 and IL-10, tumor necrosis factor (TNF)-α, toll-like receptor (TLR)-4, and alkaline phosphatase (ALP) were compared one month later, and implant infection rates were compared within 1-year follow-up. Compared with patients in the control group, the levels of Th1 and Th1/Th2 in the observation group significantly increased, yet their Th2 decreased. The levels of IL-2 and TNF-α were also observed to be significantly elevated, yet IL-10 decreased. Furthermore, their TLR-4 and ALP levels were significantly higher. Three cases of implant-related infection occurred in the control group and 1 case in the observation group. In conclusion, HBD-3 could adjust the immunity and inflammatory response of cells in the body after knee replacement, possibly playing an important role in implant-related infection.
- Delayed Cytoreductive Nephrectomy Following Three Years of Targeted Therapy for Metastatic Renal Cell Carcinoma. [Journal Article]
- CUCurr Urol 2017; 9(4):202-208
- We present a 55-year-old male, with good performance status who was diagnosed with a case of metastatic renal cell carcinoma following a pathologic femur fracture. Despite good performance status, mu...
We present a 55-year-old male, with good performance status who was diagnosed with a case of metastatic renal cell carcinoma following a pathologic femur fracture. Despite good performance status, multifocal metastases and poor-prognostic features portended a grim prognosis with predicted overall survival of less than nine months. On initial presentation, he was excluded from cytoreductive nephrectomy based on brain metastasis and interleukin-2 was not pursued as the primary tumor was to be left in situ. The patient was reconsidered for cytoreductive nephrectomy after sustained response to fifth line targeted therapies with shrinkage of tumor burden. The post-operative course was uneventful and the patient was discharged home on postoperative day one. Temsirolimus was resumed one week after surgery and the patient reported returning to his normal activities at the two week follow-up visit. We highlight important clinical features of metastatic renal cell carcinoma, the surgical considerations for cytoreductive nephrectomy and the detailed multidisciplinary care the patient received throughout this case report.
- Low interleukin-2 concentration favors generation of early memory T cells over effector phenotypes during chimeric antigen receptor T-cell expansion. [Journal Article]
- CCytotherapy 2017 Apr 11
- CONCLUSIONS: The number of early memory T cells in a T-cell preparation can be increased by simply reducing the amount of IL-2 and limiting the length of T-cell expansion, providing cells with potentially higher in vivo performance. These findings are significant for robust and cost-effective T-cell manufacturing.
New Search Next
- Enhancement of immune cytokines and splenic CD4+ T cells by electroacupuncture at ST36 acupoint of SD rats. [Journal Article]
- PlosPLoS One 2017; 12(4):e0175568
- Electroacupuncture at the ST36 acupoint can enhance the body's immune function. However, the mechanism for this enhancement has not been fully described. Our study was designed to investigate the eff...
Electroacupuncture at the ST36 acupoint can enhance the body's immune function. However, the mechanism for this enhancement has not been fully described. Our study was designed to investigate the effect of electroacupuncture on the immune function of Sprague-Dawley (SD) rats. The rats were randomly divided into three groups: a control group, a non-acupoint group (abdominal muscle acupuntured) and a ST36 acupoint group. Our results showed that successive electroacupuncture at the ST36 acupoint for 3 d significantly enhanced the interferon-γ (IFN-γ) level in the serum of SD rats. The results also showed that the serum and extracts from spleen cells of the ST36 acupoint group contained higher levels of interleukin (IL)-2 and IL-17 compared to those of the other two groups. Immunohistochemical analysis showed that electroacupuncture applied to the ST36 acupoint enhanced the expression level of CD4 in spleen cells. Furthermore, it was observed that CD4 co-localized with transient receptor potential vanilloid (TRPV) channels at the membrane of splenic CD4+ T cells and the expression level of CD4 was related to TRPV channels in the electroacupuncture treatment. These observations indicated that electroacupuncture stimulation at the ST36 acupoint enhanced the level of immune cytokines and splenic CD4+ T cells through TRPV channels in this system.