• T cell-based immunotherapy, such as immune checkpoint blockade or adoptive T cell transfer, is limited by the ability of T cells to detect major histocompatibility complex (MHC)-presented antigen by tumor cells. (elifesciences.org)
  • NK cells play a pivotal role in rapid and highly efficient cancer surveillance and represent a promising avenue for adoptive cell transfer either as a mono- or combination immunotherapy. (maxcyte.com)
  • Nevertheless, ex vivo activation with cytokines can restore cytolytic activity of NK cells against GB, indicating that NK cells have potential for adoptive immunotherapy of GB if potent cytotoxicity can be maintained in vivo . (frontiersin.org)
  • Adoptive immunotherapy using tumor-associated antigen (TAA)-specific CD8 + cytotoxic T lymphocytes (CTLs) and/or CD4 + helper T (Th) cells can induce the regression of large established tumor in not only mouse models but also cancer patients [ 1 - 3 ]. (oncotarget.com)
  • These preclinical and clinical evidences encourage us to develop T-cell adoptive immunotherapy using genetically engineered T cells that are transduced with a T-cell receptor (TCR) gene specific for TAA. (oncotarget.com)
  • The demonstration of anergic T lymphocytes following oral tolerance has so far been limited in in vitro systems, and a primary objective of the present study was to provide evidence, in vivo, for the existence of a state of anergy in mice orally fed with ovalbumin (OVA). (nih.gov)
  • Oral tolerance was induced by a single feeding with OVA, and was demonstrated by diminished antibody production in vivo, and by reduced cytokine secretion or proliferation in vitro. (nih.gov)
  • Reversal of the tolerant state in vivo was established by antibody production in irradiated mice adoptively transferred with cells cultured in the presence of rIL-2. (nih.gov)
  • The possibility that suppression was also an in vivo mechanism for tolerance was studied by adoptive transfer experiments. (nih.gov)
  • Transfer of HSV-tk to DLI preserves the beneficial anti-tumor effect and allows in vivo elimination of donor T cells if severe GvHD occurs. (haematologica.org)
  • T cells expanded ex vivo from a CpG-treated culture demonstrated potent antitumor efficacy and prolonged persistence in vivo. (bmj.com)
  • We found that tumor-intrinsic LRFN2 inhibited the recruitment and functional transition of CD8+ T cells by reducing the secretion of pro-inflammatory cytokines and chemokines, and this mechanism was verified in vitro and in vivo. (bvsalud.org)
  • We now investigate whether inhibition of Akt signaling during ex vivo expansion of CAR T cells can promote the generation of CAR T cells with enhanced antitumor activity following adoptive therapy in a murine leukemia xenograft model. (biomedcentral.com)
  • Proliferative/expansion potential, phenotypical characteristics and functionality of the propagated CD19CAR T cells were analyzed in vitro and in vivo after 17-21 day ex vivo expansion. (biomedcentral.com)
  • Manufacturing CAR T cells is a process that involves activation and ex vivo culture with IL-2 to facilitate CAR gene transfer and to achieve a therapeutic number of T cells. (biomedcentral.com)
  • However, to our knowledge, the use of agonistic antibodies to CD40 to boost adoptively transferred T cells in vivo has not been investigated. (elsevierpure.com)
  • Furthermore, purified CD4 + CD25 + cells from the SDLN of 1,25(OH) 2 D 3 -treated or UVB-irradiated mice compared with equal numbers of CD4 + CD25 + cells from control mice had increased capacity to suppress immune responses in both in vitro and in vivo assay systems. (aai.org)
  • To this end, Dr. Rosenberg and others developed a "Young TIL" approach that rapidly expands TIL for administration without in vitro selection for tumor reactivity [ 8 ], which markedly improves the timeliness of TIL production as well as its survival and efficacy in vivo (Fig. 1 ). (biomedcentral.com)
  • Here, we describe the pre-clinical in vitro and in vivo study of irradiated haNK cells engineered to express a second-generation chimeric antigen receptor (CAR) targeting programmed death-ligand 1 (PD-L1). (elifesciences.org)
  • When administrated in vivo, both intact and Fab of J43 are reported to enhance contact hypersensitivity and exacerbate acute GVHD similar to transfer of PD-1-deficient cells. (thermofisher.com)
  • The RMT4-53 antibody has been shown to block TIM-4 in vitro and in vivo . (bioxcell.com)
  • Correlating with in vivo kinetics, the peak of TIM-4 induction in lipopolysaccharide (LPS)-activated bone marrow derived-macrophages (BMM) was detected in 6-hour cultures. (bioxcell.com)
  • In this study, we demonstrate that Ab blockade of DC-expressed TIM-4 leads to increased induction of induced regulatory T cells (iTregs) from naive CD4(+) T cells, both in vitro and in vivo . (bioxcell.com)
  • Blockade of NKG2D suppresses cytolysis against ER-stressed epithelial cells in vitro and spontaneous enteritis in vivo . (bioxcell.com)
  • Results: The liver cells were found to possess preproinsulin mRNA, translate (pro)insulin in vivo and release it when exposed to 100 nmol/l glucagon in vitro. (deepdyve.com)
  • 9] has recently showed that adenovirus-medi- Materials ated in vivo transfer of the PDX-1 transgene to the mouse The PEPCK promoter was generously donated by Dr R. W. liver results in the conversion of a hepatocyte subpopula- Hanson (Case Western Reserve University, Cleveland, tion to the beta cell phenotype. (deepdyve.com)
  • The concept of enhancing cellular immunity through the transfer of ex-vivo expanded T cells was pioneered by Greenberg et al. (biomedcentral.com)
  • The aim of adoptive T-cell therapy of cancer is to selectively confer immunity against tumor cells. (haematologica.org)
  • Isolated B cells also imparted T cells with the CpG-associated phenotype and improved tumor immunity without the aid of additional antigen-presenting cells or other immune cells in the culture. (bmj.com)
  • Additionally, engineered overexpression of IRF4 in anti-tumor CD8+ T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into effector T cell states. (bvsalud.org)
  • Anti-tumor activity was evaluated after adoptive transfer of the CD19CAR T cells into CD19+ tumor-bearing immunodeficient mice. (biomedcentral.com)
  • Once adoptively transferred into CD19+ tumor-bearing mice, Akti treated CD19CAR T cells exhibited more antitumor activity than did untreated CD19CAR T cells. (biomedcentral.com)
  • Mice bearing B16 melanoma tumors expressing the gp100 tumor antigen were treated with cultured, activated T cells transgenic for a T-cell receptor specifically recognizing gp100, with or without anti-CD40 mAb. (elsevierpure.com)
  • Tumor-infiltrating lymphocyte (TIL) therapy is a type of adoptive cellular therapy by harvesting infiltrated lymphocytes from tumors, culturing and amplifying them in vitro and then infusing back to treat patients. (biomedcentral.com)
  • Its diverse TCR clonality, superior tumor-homing ability, and low off-target toxicity endow TIL therapy unique advantages in treating solid tumors compared with other adoptive cellular therapies. (biomedcentral.com)
  • After tumor excision from the patient, tumor is digested into small fragments or a single cell suspension and then expanded in culture with IL-2. (biomedcentral.com)
  • Currently, the most widely-used TIL production method is to isolate infiltrating lymphocytes from tumor tissues and then culture and expand these cells in vitro. (biomedcentral.com)
  • Early studies on the transfer of unmodified autologous or allogeneic NK cells have established their clinical safety and demonstrated modest anti-tumor efficacy. (maxcyte.com)
  • Only 10% of the human population is homozygous for this polymorphism, suggesting that genetic manipulation of NK cells to express CD16-158V prior to adoptive transfer may improve clinical success not only of NK cell therapies but also anti-tumor IgG1 antibodies. (maxcyte.com)
  • Although the efficacy of adoptive transfer of tumor infiltrating lymphocytes (TILs) was examined over several decades, genetically engineered T cells expressing chimeric antigen receptors (CARs) rapidly replaced the application of TILs due to their high specificity, non-MHC-restricted recognition of tumor antigen, superior potency, and improved in vivo persistency [ 9 , 13 , 14 ]. (biomedcentral.com)
  • Here we report that while exogenous administration of LPS was able to enhance adoptively transferred CD8 + T cells' tumor destruction, LPS treatment alone did not replace individual components of the tripartite ACT regimen, or obviate TBI. (biomedcentral.com)
  • In contrast, administering LPS after ACT potentiated the antitumor effectiveness of the regimen, thereby supporting the expansion of transferred tumor-specific CD8 + T cells over host CD4 + T cells. (biomedcentral.com)
  • Combining tumor-specific adoptive T cell therapy to the aCTLA-4/aPD1/rIL2 or aCTLA-4/aPD1/aCD137 reg-imens enhances efficacy in a synergistic manner. (unav.edu)
  • Adoptive T-cell therapy with T cell receptor (TCR) -engineered T cells is an attractive strategy for cancer treatment and the success in this therapy is dependent on the functional avidity of the transduced TCRs against targeted tumor antigens. (oncotarget.com)
  • T-cell receptor (TCR) gene transfer is an attractive strategy for rapid in vitro generation of high numbers of antigen specific T cells. (haematologica.org)
  • Although human CD20 has previously been described as functional selection marker and suicide gene after retroviral transfer to T lymphocytes, 9 , 10 the specificities of these T cells were unknown, and therefore a potential effect of CD20 on antigen-specific T-cell functions could not be investigated. (haematologica.org)
  • Insufficient persistence and effector function of chimeric antigen receptor (CAR)-redirected T cells have been challenging issues for adoptive T cell therapy. (biomedcentral.com)
  • Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. (ashpublications.org)
  • Adoptive T-cell therapy with T cells expressing chimeric antigen receptors (CARs) is an active area of cancer research. (ashpublications.org)
  • 12 , 13 Clinical trials in which patients with advanced B-cell malignancies receive T cells expressing anti-CD19 CARs are in early stages, and it is not known whether adoptive transfer of T cells targeting this self-antigen will be an effective therapy for B-cell malignancies. (ashpublications.org)
  • Anergy, as a mechanism for tolerance, was demonstrated by the ability to reverse the tolerant state after culturing tolerant cells in recombinant interleukin-2 (rIL-2). (nih.gov)
  • Results Herein we reveal a new way to reverse the tolerant state of adoptively transferred CD8 + T cells against tumors using TLR-activated B cells. (bmj.com)
  • Two of the primary immunotherapies are immune checkpoint blockade (ICB) and adoptive cell transfer (ACT). (elifesciences.org)
  • The immunomodulatory effects of vitamin D have been described following chronic oral administration to mice or supplementation of cell cultures with 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), the active form of vitamin D. In this study, topically applied 1,25(OH) 2 D 3 , enhanced the suppressive capacity of CD4 + CD25 + cells from the draining lymph nodes. (aai.org)
  • CD4 + cells from the skin-draining lymph nodes (SDLN) of either 1,25(OH) 2 D 3 -treated or UVB-irradiated mice had reduced capacity to proliferate to Ags presented in vitro, and could suppress Ag-specific immune responses upon adoptive transfer into naive mice. (aai.org)
  • B16F10-bearing mice were preconditioned with 5Gy TBI and given a tripartite ACT therapy (consisting of transferred pmel-1 CD8 + T cells, vaccination with fowlpox encoding gp100, and IL-2) along with TLR4 agonist LPS. (biomedcentral.com)
  • To investigate the interrelation between Treg and neutrophils in the leukemia microenvironment, we performed experiments using TCL1-injected DEREG mice with Treg depletion or RAG2KO mice with adoptively transferred TCL1 cells alone or together with Treg. (biomedcentral.com)
  • Adoptive transfer of Sig-1R intact macrophages to recipient Sig-1R knockout mice with tMCAO was developed to observe its effect on apoptotic neuron clearance and stroke outcomes. (thno.org)
  • Adoptive transfer of Sig-1R intact bone marrow-derived macrophages (BMDMs) to Sig-1R knockout mice restored the clearance activity of dead/dying neurons, reduced infarct area and neuroinflammation, and improved long-term functional recovery after cerebral ischemia. (thno.org)
  • TIL therapy is a type of adoptive cellular therapy leveraging the patient's own immune system to treat tumors. (biomedcentral.com)
  • CD20-transduced T cells with and without co-transferred T-cell receptor were efficiently eliminated by complement dependent cytotoxicity induced by therapeutic anti-CD20 antibody rituximab. (haematologica.org)
  • The purpose of this study was to determine whether anti-CD40 monoclonal antibody (mAb) in combination with interleukin (IL)-2 could improve the efficacy of in vitro-activated T cells to enhance antitumor activity. (elsevierpure.com)
  • 3 Autologous lymphocytes genetically modified with the TCR for MART-1/Melan-A have been adoptively transferred to patients with advanced melanoma. (haematologica.org)
  • Thereafter the adverse effects of such intravenously administered cytokines lead to the extraction of the lymphocytes from the blood and culture-expand them in the lab and then to inject the cells alone enable them destroy the cancer cells. (wikipedia.org)
  • Cell-mediated immune responses are initiated by T lymphocytes that are themselves stimulated by cognate peptides bound to MHC molecules on antig en-presenting cells (APC). (thermofisher.com)
  • Thus, when cultured alone without special treatment, CLL cells do not proliferate under in vitro conditions. (biomedcentral.com)
  • To evaluate anti-CD19-CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. (ashpublications.org)
  • To establish a murine model in which a completely syngeneic lymphoma could be treated by adoptive transfer of syngeneic CAR-transduced T cells, we developed a CAR that could specifically recognize murine CD19. (ashpublications.org)
  • In vitro cytotoxic activity against rituximab-coated CD20+ B cell lymphoma cells of CD16-engineered or non-engineered NK cells was assessed 24 hours post electroporation. (maxcyte.com)
  • LRFN2 restrained antitumor immunity by inhibiting the infiltration, proliferation, and differentiation of CD8+ T cells in vitro. (bvsalud.org)
  • Background Adoptive T cell transfer (ACT) therapy improves outcomes in patients with advanced malignancies, yet many individuals relapse due to the infusion of T cells with poor function or persistence. (bmj.com)
  • While increased CD16 expression was transient in nature, this may not negatively impact the therapeutic potential of engineered NK cells due to the short persistence of adoptively transferred NK cells. (maxcyte.com)
  • Autologous immune enhancement therapy (AIET) is a treatment method in which immune cells are taken out from the patient's body which are cultured and processed to activate them until their resistance to cancer is strengthened and then the cells are put back in the body. (wikipedia.org)
  • We found that Akt inhibition did not compromise CD19CAR T cell proliferation and expansion in vitro, independent of the T cell subsets, as comparable CD19CAR T cell expansion was observed after culturing in the presence or absence of Akt inhibitor. (biomedcentral.com)
  • Co-transfer of a suicide gene would provide a desirable safety switch in clinical TCR gene therapy. (haematologica.org)
  • Non-viral engineering of NK cells using MaxCyte ® mRNA electroporation provides significant benefits including high efficiency and low toxicity as well as clinical scalability enabling rapid development of novel adoptive cell therapy approaches. (maxcyte.com)
  • Music has an important role in all human cultures and has been found to have direct and indirect effects on physiologic functions and clinical symptoms. (e-lub.net)
  • Lymphodepletion enhances adoptive T cell transfer (ACT) therapy by activating the innate immune system via microbes released from the radiation-injured gut. (biomedcentral.com)
  • We develop a multifocal HCC model to test immunotherapies by introducing c-myc using hydrodynamic gene transfer along with CRISPR-Cas9-mediated disruption of p53 in mouse hepatocytes. (unav.edu)
  • Adoptive Immuno cell therapy of cancer was first introduced by Steven Rosenberg and his colleagues of National Institute of Health USA. (wikipedia.org)
  • Collectively, these findings provide a rationale to evaluate the potential application of anti-CD40 mAb in adoptive T-cell therapy for cancer. (elsevierpure.com)
  • In cultured primary fibroblasts and cancer cells, the chemotherapeutic drug doxorubicin causes mtDNA damage and release, which leads to cGAS STING dependent ISG activation. (regenerativemedicine.net)
  • 15 We have recently conducted experiments that demonstrated enhanced in vitro survival of human T cells that were transduced with an ErbB2-specific CAR when the first and third ITAMs of the CD3-ζ domain of the CAR were inactivated. (ashpublications.org)
  • In the present study, cell lineage tracing studies by adoptive transfer of GFP+ or dye-labelled macrophages identified that monocyte/macrophages from bone marrow can give rise to myofibroblasts via the process of macrophage-myofibroblast transition (MMT) in a mouse model of unilateral ureteric obstruction. (oncotarget.com)
  • In vitro studies in Smad3 null bone marrow macrophages also showed that Smad3 was required for TGF-β1-induced MMT and collagen production. (oncotarget.com)
  • 4 In addition, TCRs for minor histocompatibility antigens, including HA-1 and HA-2, have been transferred to donor-derived virus-specific T cells to treat patients with hematologic malignancies after allogeneic stem cell transplantation. (haematologica.org)
  • The data support the broad value of CD20 as safety switch in adoptive T-cell therapy. (haematologica.org)
  • In this study, we investigated the use of CD20 as safety switch after retroviral transfer to T cells with different cytomegalovirus (CMV) specificities, and conclude that CD20 may be broadly applicable as safeguard in adoptive T-cell therapy. (haematologica.org)
  • Furthermore, the expression of CD40 on bone marrow-derived cells and the presence of CD80/CD86 in the host were required for the expansion of adoptively transferred T cells. (elsevierpure.com)
  • In this model, the combination of anti-CD40 mAb with IL-2 led to expansion of adoptively transferred T cells and induced a more robust antitumor response. (elsevierpure.com)
  • The use of neutralizing mAb to IL-12 provided direct evidence that enhanced IL-12 secretion induced by anti-CD40 mAb was crucial for the expansion of adoptively transferred T cells. (elsevierpure.com)