scholarly journals Cell Transfer Therapy for Cancer: Past, Present, and Future

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoling Qian ◽  
Xian Wang ◽  
Hongchuan Jin
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Human Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Transfer ◽  
Human Cancer Cells ◽  
Cancer Tissues ◽  
Infiltrating Lymphocytes

Cell transfer therapy for cancer has made a rapid progress recently and the immunotherapy has been recognized as the fourth anticancer modality after operation, chemotherapy, and radiotherapy. Lymphocytes used for cell transfer therapy include dendritic cells, natural killer (NK) cells, and T lymphocytes such as tumor-infiltrating lymphocytes (TILs) and cytotoxic T lymphocytes (CTLs). In vitro activated or engineered immune cells can traffic to cancer tissues to elicit persistent antitumor immune response which is very important especially after immunosuppressive treatments such as chemotherapy. In this review, we overviewed recent advances in the exploration of dendritic cells, NK cells, and T cells for the treatment of human cancer cells.

scholarly journals Cellular and gene signatures of tumor-infiltrating dendritic cells and natural-killer cells predict prognosis of neuroblastoma

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ombretta Melaiu ◽  
Marco Chierici ◽  
Valeria Lucarini ◽  
Giuseppe Jurman ◽  
Libenzio Adrian Conti ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Infiltrating Lymphocytes ◽  
Gene Signatures ◽  
Protein Levels ◽  
T Cell Infiltration ◽  
Clinical Biomarkers ◽  
Infiltrating Lymphocytes

AbstractTumor-infiltrating lymphocytes play an essential role in improving clinical outcome of neuroblastoma (NB) patients, but their relationship with other tumor-infiltrating immune cells in the T cell-inflamed tumors remains poorly investigated. Here we show that dendritic cells (DCs) and natural killer (NK) cells are positively correlated with T-cell infiltration in human NB, both at transcriptional and protein levels, and associate with a favorable prognosis. Multiplex imaging displays DC/NK/T cell conjugates in the tumor microenvironment of low-risk NB. Remarkably, this connection is further strengthened by the identification of gene signatures related to DCs and NK cells able to predict survival of NB patients and strongly correlate with the expression of PD-1 and PD-L1. In summary, our findings unveil a key prognostic role of DCs and NK cells and indicate their related gene signatures as promising tools for the identification of clinical biomarkers to better define risk stratification and survival of NB patients.

Generation and characterization of antitumor infiltrating lymphocytes from patients with breast cancer for adoptive cell transfer therapy.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 145-145
Author(s):  
Juhua Zhou ◽  
Yin Zhong ◽  
Zhongjun Hou ◽  
Jianzhong Zhang ◽  
Yanmin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Adoptive Cell Transfer ◽  
Autologous Tumor ◽  
Cell Transfer ◽  
Adoptive Cell Transfer Therapy ◽  
Infiltrating Lymphocytes

145 Background: Clinical trials have shown that adoptive cell transfer therapy is a promising method for cancer treatment. In the current study, we aim to generate and characterize anti-tumor tumor-infiltrating lymphocytes from patients with breast cancer for adoptive cell transfer therapy. Methods: In vitro culture method was used to generate anti-tumor, tumor-infiltrating lymphocytes from patients with breast cancer. FACS analysis, ELISA, and Elispot assay were used to characterize tumor-infiltrating lymphocytes. Autologous anti-tumor tumor-infiltrating lymphocytes from patients with breast cancer were used in adoptive cell transfer therapy. Results: FACS analysis indicated that tumor-infiltrating lymphocytes were present in the tumor tissues, but not detectable in the normal breast tissues from patients with breast cancer. Tumor-infiltrating lymphocytes could be generated in vitro from fresh tumor specimens of patients with breast cancer. Both CD4 T cells and CD8 T cells were detected in tumor-infiltrating lymphocytes. Autologous tumor cells could also generate in vitro from fresh tumor tissue samples of patients with breast cancer. Among 22 samples screened, 6 samples (25%) of tumor-infiltrating lymphocytes are tumor-reactive. Anti-tumor, tumor-infiltrating lymphocytes could recognize autologous tumor cells and allogenic tumor cells. After a large scale T cell expansion, anti-tumor reactivity was maintained in tumor-infiltrating lymphocytes. All of tumor-infiltrating lymphocytes were NK cells in some samples from patients with breast cancer, and these NK cells could recognize autologous tumor cells and a panel of allogenic tumor cells. T cell cloning assay demonstrated that some of the tumor-reactive, tumor-infiltrating lymphocytes were CD4 T cells. Conclusions: The results suggest that anti-tumor, tumor-infiltrating lymphocytes may be generated from patients with breast cancer, which may be used in clinical applications of adoptive cell transfer therapy for patients with breast cancer. The clinical trial of adoptive cell transfer therapy using autologous anti-tumor tumor-infiltrating lymphocytes for patients with breast is under way.

Proteasome Inhibitor Does Not Affect the Function of Human Immune Systems: Effects on Dendritic Cells, T Lymphocytes and NK Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3930-3930
Author(s):  
Jooeun E. Bae ◽  
Tai Yu-Tzu ◽  
Teru Hidesima ◽  
Larence Catley ◽  
Xianfeng Li ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Immune Function ◽  
Nk Cells ◽  
Proteasome Inhibitor ◽  
Antigen Expression ◽  
Antigen Uptake ◽  
Human Immune

Abstract Bortezomib is the first proteasome inhibitor approved for the therapy of multiple myeloma (MM) based on its in vitro and in vivo activity in myeloma. However, the toxicity and effects of this drug on the human immune function have not been entirely studied. In the present study, we evaluated the effects of Bortezomib on normal human immune cells including dendritic cells (DC), T lymphocytes and NK cells for cell survival, antigen expression, production of cytokines, and other key parameters of immune cell function. In our evaluation of effect of Bortezomib on DC, we did not observe significant change in the expression of cell surface antigens including CD40, CD80, CD83, CD86, HLA-ABC and HLA-DPQR molecules in terms of percentage of cells positive as well as mean fluorescence intensity (MFI). Bortezomib treated immature DC maintained the ability for antigen uptake as measured by uptake of Dextran-FITC (untrt vs. trt = 798 MFI vs. 802 MFI), maintained the expression levels of antigen uptake receptors including mannose (untrt vs. trt = 85% vs. 79%) and DEC-205 (untrt vs. trt = 49% vs. 42%), and the capacity to produce IL-12 (untrt vs. trt = 135 vs. 125 pg/ml). In addition, Bortezomib treated mature DC was able to induce comparable levels of allogenic T cell proliferation to the untreated mature DC as measured by 3[H]-Thymidine incorporation (untrt vs. trt = 212556 cpm vs. 220571 cpm). Furthermore, cell surface antigen expression including CD3, CD4, CD8, CD28, CD154 (CD40L) and TCRab on T lymphocytes were not changed by Bortezomib treatment. The treated T cells also maintained the ability to secrete IFN-g secretion in response to allogenic DC (untrt vs. trt = 85 vs. 88 pg/ml) or Staphylococcal enterotoxin B (untrt vs. trt = 131 vs. 154 pg/ml). The cytolytic activity of the NK cell population was comparable between proteasome inhibitor treated and untreated control cells against the McCAR (untrt vs. trt = 44% vs. 52%) and MM1S (49% vs. 42%) target MM cell lines. This observation was correlated with similar expression levels of CD2, CD11a, CD94, NKp30, NKp44, NKp46, and KARp50.3 activation antigens in treated versus untreated NK cells. These, in vitro results confirm lack of adverse effects of Bortezomib on immune function, and allow us to incorporate of Bortezomib in multimodality therapy that includes immunotherapy.

scholarly journals The Ovarian Cancer Tumor Immune Microenvironment (TIME) as Target for Therapy: A Focus on Innate Immunity Cells as Therapeutic Effectors

2020 ◽  
Vol 21 (9) ◽  
pp. 3125 ◽  
Author(s):  
Denisa Baci ◽  
Annalisa Bosi ◽  
Matteo Gallazzi ◽  
Manuela Rizzi ◽  
Douglas M. Noonan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Lymphocytes ◽  
Nk Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Microenvironment ◽  
New Era ◽  
Tumor Immune Microenvironment ◽  
Cancer Tumor ◽  
Immune Contexture ◽  
Infiltrating Lymphocytes

Ovarian cancer (OvCA) accounts for one of the leading causes of death from gynecologic malignancy. Despite progress in therapy improvements in OvCA, most patients develop a recurrence after first-line treatments, dependent on the tumor and non-tumor complexity/heterogeneity of the neoplasm and its surrounding tumor microenvironment (TME). The TME has gained greater attention in the design of specific therapies within the new era of immunotherapy. It is now clear that the immune contexture in OvCA, here referred as tumor immune microenvironment (TIME), acts as a crucial orchestrator of OvCA progression, thus representing a necessary target for combined therapies. Currently, several advancements of antitumor immune responses in OvCA are based on the characterization of tumor-infiltrating lymphocytes, which have been shown to correlate with a significantly improved clinical outcome. Here, we reviewed the literature on selected TIME components of OvCA, such as macrophages, neutrophils, γδ T lymphocytes, and natural killer (NK) cells; these cells can have a role in either supporting or limiting OvCA, depending on the TIME stimuli. We also reviewed and discussed the major (immune)-therapeutic approaches currently employed to target and/or potentiate macrophages, neutrophils, γδ T lymphocytes, and NK cells in the OvCA context.

Structure-Reactivity Relationships on Substrates and Inhibitors of the Lysine Deacylase Sirtuin 2 from Schistosoma Mansoni (SmSirt2)

2019 ◽  
Author(s):  
Daria Monaldi ◽  
Dante Rotili ◽  
Julien Lancelot ◽  
Martin Marek ◽  
Nathalie Wössner ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Human Cancer ◽  
Egg Laying ◽  
Human Cancer Cells ◽  
Parasite Survival ◽  
Survival And Reproduction ◽  
Emergence Of Resistance ◽  
First Time ◽  
Parasitic Life Cycle

The only drug for treatment of Schistosomiasis is Praziquantel, and the possible emergence of resistance makes research on novel therapeutic agents necessary. Targeting of Schistosoma mansoni epigenetic enzymes, which regulate the parasitic life cycle, emerged as promising approach. Due to the strong effects of human Sirtuin inhibitors on parasite survival and reproduction, Schistosoma sirtuins were postulated as therapeutic targets. In vitro testing of synthetic substrates of S. mansoni Sirtuin 2 (SmSirt2) and kinetic experiments on a myristoylated peptide demonstrated lysine long chain deacylation as an intrinsic SmSirt2 activity for the first time. Focused in vitro screening of the GSK Kinetobox library and structure-activity relationships (SAR) of identified hits, led to the first SmSirt2 inhibitors with activity in the low micromolar range. Several SmSirt2 inhibitors showed potency against both larval schistosomes (viability) and adult worms (pairing, egg laying) in culture without general toxicity to human cancer cells.<br>

scholarly journals A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

2021 ◽  
Vol 22 (16) ◽  
pp. 8372
Author(s):  
Ana María Zárate ◽  
Christian Espinosa-Bustos ◽  
Simón Guerrero ◽  
Angélica Fierro ◽  
Felipe Oyarzún-Ampuero ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Antitumour Activity ◽  
Anticancer Compounds ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis Inducer ◽  
Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

scholarly journals C4b-binding protein α-chain enhances antitumor immunity by facilitating the accumulation of tumor-infiltrating lymphocytes in the tumor microenvironment in pancreatic cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Kosuke Sasaki ◽  
Shigetsugu Takano ◽  
Satoshi Tomizawa ◽  
Yoji Miyahara ◽  
Katsunori Furukawa ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Binding Protein ◽  
Combined Treatment ◽  
Tumor Infiltrating Lymphocytes ◽  
Pdac Cell ◽  
Α Chain ◽  
Infiltrating Lymphocytes

Abstract Background Recent studies indicate that complement plays pivotal roles in promoting or suppressing cancer progression. We have previously identified C4b-binding protein α-chain (C4BPA) as a serum biomarker for the early detection of pancreatic ductal adenocarcinoma (PDAC). However, its mechanism of action remains unclear. Here, we elucidated the functional roles of C4BPA in PDAC cells and the tumor microenvironment. Methods We assessed stromal C4BPA, the C4BPA binding partner CD40, and the number of CD8+ tumor-infiltrating lymphocytes in resected human PDAC tissues via immunohistochemical staining. The biological functions of C4BPA were investigated in peripheral blood mononuclear cells (PBMCs) and human PDAC cell lines. Mouse C4BPA (mC4BPA) peptide, which is composed of 30 amino acids from the C-terminus and binds to CD40, was designed for further in vitro and in vivo experiments. In a preclinical experiment, we assessed the efficacy of gemcitabine plus nab-paclitaxel (GnP), dual immune checkpoint blockades (ICBs), and mC4BPA peptide in a mouse orthotopic transplantation model. Results Immunohistochemical analysis revealed that high stromal C4BPA and CD40 was associated with favorable PDAC prognosis (P=0.0005). Stromal C4BPA strongly correlated with the number of CD8+ tumor-infiltrating lymphocytes (P=0.001). In in vitro experiments, flow cytometry revealed that recombinant human C4BPA (rhC4BPA) stimulation increased CD4+ and CD8+ T cell numbers in PBMCs. rhC4BPA also promoted the proliferation of CD40-expressing PDAC cells. By contrast, combined treatment with gemcitabine and rhC4BPA increased PDAC cell apoptosis rate. mC4BPA peptide increased the number of murine T lymphocytes in vitro and the number of CD8+ tumor-infiltrating lymphocytes surrounding PDAC tumors in vivo. In a preclinical study, GnP/ICBs/mC4BPA peptide treatment, but not GnP treatment, led to the accumulation of a greater number of CD8+ T cells in the periphery of PDAC tumors and to greater tumor regression than did control treatment. Conclusions These findings demonstrate that the combination of GnP therapy with C4BPA inhibits PDAC progression by promoting antitumor T cell accumulation in the tumor microenvironment.

Rhodium(i) N-heterocyclic carbene complexes: synthesis and cytotoxic properties

2021 ◽  
Vol 45 (11) ◽  
pp. 5176-5183
Author(s):  
Ichraf Slimani ◽  
Serap Şahin-Bölükbaşı ◽  
Mustafa Ulu ◽  
Enes Evren ◽  
Nevin Gürbüz ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mtt Assay ◽  
Incubation Time ◽  
Human Cancer ◽  
Cytotoxic Activities ◽  
Carbene Complexes ◽  
Human Cancer Cells ◽  
Benzimidazolium Salts ◽  
Ht 29

A series of benzimidazolium salts and their [RhCl(NHC)(COD)] complexes were synthesized. All compounds were screened for in vitro cytotoxic activities against a panel of human cancer cells (HT-29 colon, Ishikawa endometrial, U-87 glioblastoma) using the MTT assay for 48 h incubation time.

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