Search results for: CD8 antibody, Monoclonal Antibodies, Host Mouse
#29123966 // Save this To Up
PD-1 blockade at the time of tumor escape potentiates the immune-mediated antitumor effects of a melanoma-targeting monoclonal antibody.Tumor antigen-targeting monoclonal antibodies (TA-targeting mAbs) are used as therapeutics in many malignancies and their capacity to mobilize the host immunity puts them at the forefront of anti-cancer immunotherapies. Both innate and adaptive immune cells have been associated with the therapeutic activity of such antibodies, but tumor escape from mAb-induced tumor immune surveillance remains one of the main clinical issues. In this preclinical study, we grafted immunocompetent and immunocompromised mice with the B16F10 mouse melanoma cell line and treated them with the TA99 TA-targeting mAb to analyze the immune mechanisms associated with the tumor response and resistance to TA99 monotherapy. In immunocompetent mice TA99 treatment strongly increased the fraction of CD8 and CD4 effector T cells in the tumor compared with isotype control, highlighting the specific immune modulation of the tumor microenvironment by TA99. However, in most mice, TA99 immunotherapy could not prevent immune effector exhaustion and the recruitment of regulatory CD4 T cells and consequently tumor escape from immune surveillance. Remarkably, anti-PD-1 treatment at the time of tumor emergence restored the Th1 effector functions of CD4 and CD8 T cells as well as of natural killer and γδT cells, which translated into a significant slow-down of tumor progression and extended survival. Our findings provide the first evidence that PD-1 blockade at the time of tumor emergence can efficiently boost the host anti-tumor immune response initiated several weeks before by the TA-targeting mAb. These results are promising for the design of combined therapies to sensitize non-responder or resistant patients.
1124 related Products with: PD-1 blockade at the time of tumor escape potentiates the immune-mediated antitumor effects of a melanoma-targeting monoclonal antibody.TCP-1 theta antibody Sour FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu Normal mouse multiple org Purified Mouse Anti Human Purified Mouse Anti Human Monoclonal Anti-ATP Synth Monoclonal Anti-ATIC prod Monoclonal Anti-ATM produ Monoclonal Anti-ATM produ Monoclonal Anti-ATM produ
#29093083 // Save this To Up
Dynamics of Sendai Virus Spread, Clearance, and Immunotherapeutic Efficacy after Hematopoietic Cell Transplant Imaged Noninvasively in Mice.There are no approved vaccines or virus-specific treatments for human parainfluenza viruses (HPIVs), which have recently been reclassified into the species,,, andThese viruses cause morbidity and mortality in immunocompromised patients, including those undergoing hematopoietic cell transplant (HCT). No small-animal models for noninvasive imaging of respiratory virus infection in the HCT host exist, despite the utility that such a system would offer to monitor prolonged infection, its clearance, and treatment options. We used a luciferase-expressing reporter virus to noninvasively image in mice the infection of murine respirovirus (strain Sendai virus [SeV]), the murine counterpart of HPIV1. Independent of disease severity, the clearance of infection began approximately 21 days after HCT, largely due to the recovery of CD8T cells. Immunotherapy with granulocyte colony-stimulating factor (G-CSF) and adoptive transfer of natural killer (NK) cells provided a limited therapeutic benefit. Treatment with a fusion (F) protein-specific monoclonal antibody arrested the spread of lung infection and reduced the disease severity even when treatment was delayed to up to 10 days postinfection but had little observable effect on upper respiratory tract infection. Adoptive transfer of virus-specific T cells at 10 days postinfection accelerated the clearance by 5 days, reduced the extent of infection throughout the respiratory tract, and reduced the disease severity. Overall, the results support investigation of the clinical treatment of respiratory virus infection in the HCT host with monoclonal antibodies and adoptive T-cell transfer; the imaging system should be extendable to other respiratory viruses, such as respiratory syncytial virus and influenza virus.Parainfluenza viruses are a major cause of disease and death due to respiratory virus infection in the immunocompromised host, including those undergoing bone marrow transplantation. There are currently no effective treatment measures. We noninvasively imaged mice that were undergoing a bone marrow transplant and infected with Sendai virus, a murine parainfluenza virus (respirovirus). For the first time, we show the therapeutic windows of adoptive T-cell therapy and treatment with a monoclonal antibody to the fusion (F) protein in clearing Sendai virus from the respiratory tract and reducing disease severity. Mice tolerated these treatments without any detectable toxicity. These findings pave the way for studies assessing the safety of T-cell therapy against parainfluenza virus in humans. Adoptive T-cell therapy against other blood-borne viruses in humans has been shown to be safe and effective. Our model of noninvasive imaging in mice that had undergone a bone marrow transplant may be well suited to track other respiratory virus infections and develop novel preventive and therapeutic strategies.
2582 related Products with: Dynamics of Sendai Virus Spread, Clearance, and Immunotherapeutic Efficacy after Hematopoietic Cell Transplant Imaged Noninvasively in Mice.Anti C Reactive Protein A anti HSV (II) gB IgG1 (mo anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl CELLKINES Natural Human I CELLKINES INTERLEUKIN 2 ( CELLKINES INTERLEUKIN 2 ( Human Epstein-Barr Virus Jurkat Cell Extract (Indu Jurkat Cell Extract (Indu Jurkat Cell Extract (Indu Jurkat Cell Extract (Indu
#28787768 // Save this To Up
Combination of anti-CD4 antibody treatment and donor lymphocyte infusion ameliorates graft-versus-host disease while preserving graft-versus-tumor effects in murine allogeneic hematopoietic stem cell transplantation.Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not only a well-established immunotherapy for hematologic malignancies, but is potentially useful for treating solid tumors refractory to available therapies. However, application of allo-HSCT to solid tumors is limited, despite the beneficial antitumor effects, by the risk of graft-versus-host disease (GVHD). CD4T cells have been implicated in several aspects of GVHD, and suppress antitumor CD8T-cell responses. In the present study, we investigated clinically applicable allo-HSCT protocols designed to maximize antitumor effects while reducing the risk of GVHD. We used a mouse model of allo-HSCT with s.c. tumors. We found that myeloablative conditioning was associated with better inhibition of tumor growth but with severe acute GVHD. Early treatment with anti-CD4 mAb substantially ameliorated GVHD while preserving antitumor effects, leading to improved survival in myeloablative allo-HSCT. Late treatment with anti-CD4 mAb also ameliorated GVHD to some extent. Donor lymphocyte infusion in GVHD mice treated with anti-CD4 mAb further suppressed tumor growth without exacerbating GVHD. Collectively, our results suggest that myeloablative allo-HSCT followed by anti-CD4 mAb treatment and donor lymphocyte infusion could be a potent and safe immunotherapy for patients with cancers refractory to available therapies.
2330 related Products with: Combination of anti-CD4 antibody treatment and donor lymphocyte infusion ameliorates graft-versus-host disease while preserving graft-versus-tumor effects in murine allogeneic hematopoietic stem cell transplantation.Anti 3 DG imidazolone Mon Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph Rabbit Anti-Integrin alph
#28746799 // Save this To Up
Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy.Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In the present study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8T cells. We further evaluated the immune status of tumor microenvironments and confirmed that mature dendritic cells, helper T cells and cytotoxic T cells were highly accumulated in tumor sites under the IL-6-deficient condition. In addition, higher numbers of interferon (IFN)-γ-producing T cells were present in the tumor tissues of IL-6-deficient mice compared with wild-type mice. Surface expression levels of programmed death-ligand 1 (PD-L1) and MHC class I on CT26 cells were enhanced under the IL-6-deficient condition in vivo and by IFN-γ stimulation in vitro. Finally, we confirmed that in vivo injection of an anti-PD-L1 antibody or a Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid, effectively inhibited tumorigenesis under the IL-6-deficient condition. Based on these findings, we speculate that a lack of IL-6 produced in tumor-bearing host augments induction of antitumor effector T cells and inhibits tumorigenesis in vivo, suggesting that IL-6 signaling may be a promising target for the development of effective cancer immunotherapies.
2124 related Products with: Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy.Rabbit anti PKC theta (Ab Rabbit anti PKC theta (Ab Rabbit anti PKC theta (Ab Breast cancer tissue arra Liver cancer tissue array Theobromine CAS Number [8 Multiple cancer (12 type) Multiple cancer (12 type) Multiple organ cancer tis Multiple organ tumor tiss Tissue array of ovarian g CELLKINES INTERLEUKIN 2 (
#28498033 // Save this To Up
Development and Characterization of Novel Monoclonal Antibodies Against Human DNAM-1.DNAM-1 (CD226) is an activating immunoreceptor expressed on lymphocytes and myeloid cells. CD155 and CD112 are the ligands for DNAM-1. DNAM-1 plays an important role in tumor immunity mediated by CD8T cells and NK cells. Moreover, the interaction of DNAM-1 with the ligands contributed to the development of acute graft versus host disease (GVHD) and treatment with anti-DNAM-1 monoclonal antibodies (mAb) dramatically improved acute GVHD in a mouse model, suggesting that DNAM-1 may be a good molecular target for therapy to acute GVHD in human. In this study, we generated and characterized five novel clones of anti-human DNAM-1 mAbs, named TX94, TX95, TX96, TX107, and TX108. Among these mAbs, TX94 is a unique neutralizing mAb that most efficiently blocked the interaction between DNAM-1 and CD155. Furthermore, TX94 inhibited NK cell-mediated cytotoxicity against a tumor cell line and suppressed CD8T cell proliferation mediated by allogeneic mixed lymphocyte reaction. Thus, TX94 may be useful for molecular therapy targeting DNAM-1.
2985 related Products with: Development and Characterization of Novel Monoclonal Antibodies Against Human DNAM-1.Anti AGO2 Human, Monoclon Anti AGO2 Human, Monoclon Anti Human AGO3, Monoclon Human IgM antibody, Monoc Human IgG antibody, Monoc Human IgA antibody, Monoc Human IgE antibody, Monoc Human Serum Albumin antib Human Serum Albumin antib Human Growth Hormone anti Human Growth Hormone anti Human Growth Hormone anti
#28490665 // Save this To Up
In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy.Monoclonal antibodies (mAbs) targeting the immune checkpoint anti-programmed cell death protein 1 (aPD-1) have demonstrated impressive benefits for the treatment of some cancers; however, these drugs are not always effective, and we still have a limited understanding of the mechanisms that contribute to their efficacy or lack thereof. We used in vivo imaging to uncover the fate and activity of aPD-1 mAbs in real time and at subcellular resolution in mice. We show that aPD-1 mAbs effectively bind PD-1tumor-infiltrating CD8T cells at early time points after administration. However, this engagement is transient, and aPD-1 mAbs are captured within minutes from the T cell surface by PD-1tumor-associated macrophages. We further show that macrophage accrual of aPD-1 mAbs depends both on the drug's Fc domain glycan and on Fcγ receptors (FcγRs) expressed by host myeloid cells and extend these findings to the human setting. Finally, we demonstrate that in vivo blockade of FcγRs before aPD-1 mAb administration substantially prolongs aPD-1 mAb binding to tumor-infiltrating CD8T cells and enhances immunotherapy-induced tumor regression in mice. These investigations yield insight into aPD-1 target engagement in vivo and identify specific Fc/FcγR interactions that can be modulated to improve checkpoint blockade therapy.
2564 related Products with: In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy.Goat Anti-Human Tissue Fa Brain tumor tissue array Multiple organ tumor with Liver tumor tissue array, Pancreas tumor test tissu Brain tumor tissue array Skin tumor tissue array, Anti AGO2 Human, Monoclon Anti AGO2 Mouse, Monoclon anti HCMV IE pp65 IgG1 (m anti HCMV gB IgG1 (monocl Goat Anti- TRPM8, (intern
#28359782 // Save this To Up
In vivo IL-4 prevents allo-antigen driven CD8CTL development.IL-4 has been shown to suppress acute graft vs. host disease (GVHD) in irradiated hosts. Here we evaluated whether IL-4 suppresses acute GVHD in the un-irradiated parent-into-F1 GVHD model with relevance to renal allograft rejection. IL-4 completely suppressed CD8 CTL when administered with donor cells however this effect was lost if its administration was delayed 3days. IL-4 did not inhibit donor CD8T cell homing to the host spleen but rather prevented donor CD8T cell differentiation into CTLs. Studies with IL-4Rα-deficient donor cells or recipient mice demonstrated that IL-4 effects on the host, rather than, or in addition to IL-4 effects on donor cells, were critical for suppression of CTL. Because IL-4 decreased all splenic dendritic cell populations and increased neutrophil and CD8T cells, IL-4 may suppress donor CD8CTL by decreasing Ag presentation and/or increasing host myeloid and CD8T cell suppression of donor T cells.
Directed In Vivo Angiogen Mouse Anti-Insulin-Like G HIV 1 gag p24 recombinant HIV 1 env gp41 recombinan HEV (Birma) ORF2 recombin HAV VP3 recombinant antig Recombinant Viral antige Recombinant Viral antige SARS Associated Coronavir HIV 1 intergase antigen. VZV gE recombinant antige HLTV I envelope recombina
#28259002 // Save this To Up
Enhanced humoral and CD8+ T cell immunity in mice vaccinated by DNA vaccine against human respiratory syncytial virus through targeting the encoded F protein to dendritic cells.Human respiratory syncytial virus (RSV) is the most important cause of serious lower respiratory tract infection in infants, the elderly, and the immunocompromised population. There is no licensed vaccine against RSV until now. It has been reported that targeting antigen to DEC205, a phagocytosis receptor on dendritic cells (DCs), could induce enhanced CD4+ and CD8+ T cell responses in mice. To develop RSV DNA vaccine and target the encoded antigen protein to DCs, the ectodomain of fusion glycoprotein (sF, amino acids: 23-524) of RSV was fused with anti-DEC205 single-chain Fv fragment (scDEC) and designated scDECF. Following successful expression from the recombinant plasmid of pVAX1/scDECF, the recombinant protein of scDECF was found capable of specifically binding to DEC205 receptor on CHOmDEC205 cells, and facilitating uptake of RSV F by DC2.4 cells in vitro. Furthermore, the higher levels of RSV-specific IgG antibody responses and neutralization antibody titers, as well as RSV F-specific CD8+ T cell responses were induced in mice immunized intramuscularly by pVAX1/scDECF than by the control plasmid of pVAX1/scISOF encoding sF protein fused with isotype matched control single-chain Fv fragment (scISO). Compared with pVAX1/scISOF, both the ratio of IgG2a/IgG1, >1, and the enhanced IFN-γ cytokine were induced in mice following pVAX1/scDECF immunization, which exhibited a Th1 dominant response in pVAX1/scDECF vaccinated mice. Notably, the elevated efficiency of RSV F protein bound by DCs in vivo could also be observed in mice inoculated by pVAX1/scDECF. Collectively, these results demonstrate the enhanced IgG and CD8T cell immune responses have been induced successfully by DNA vaccine against RSV by targeting F antigen to DCs via the DEC205 receptor, and this DC-targeting vaccine strategy merits further investigation.
1796 related Products with: Enhanced humoral and CD8+ T cell immunity in mice vaccinated by DNA vaccine against human respiratory syncytial virus through targeting the encoded F protein to dendritic cells.Anti C Reactive Protein A Human Tonsil Microvascula Human Dnak (HSP70) His ta FIV Core Ag, recombinant Macrophage Colony Stimula Macrophage Colony Stimula Recombinant Human OPG TNF Recombinant Human OPG TNF Recombinant Human THPO [f Cell Meter™ Fluorimetri Cell Meter™ Fluorimetri thymic dendritic cell-der
#28153727 // Save this To Up
CD40 agonist converting CTL exhaustion via the activation of the mTORC1 pathway enhances PD-1 antagonist action in rescuing exhausted CTLs in chronic infection.Expansion of PD-1-expressing CD8cytotoxic T lymphocytes (CTLs) and associated CTL exhaustion are chief issues for ineffective virus-elimination in chronic infectious diseases. PD-1 blockade using antagonistic anti-PD-L1 antibodies results in a moderate conversion of CTL exhaustion. We previously demonstrated that CD40L signaling of ovalbumin (OVA)-specific vaccine, OVA-Texo, converts CTL exhaustion via the activation of the mTORC1 pathway in OVA-expressing adenovirus (AdVova)-infected B6 mice showing CTL inflation and exhaustion. Here, we developed AdVova-infected B6 and transgenic CD11c-DTR (termed AdVova-B6 and AdVova-CD11c-DTR) mice with chronic infection, and assessed a potential effect of CD40 agonist on the conversion of CTL exhaustion and on a potential enhancement of PD-1 antagonist action in rescuing exhausted CTLs in our chronic infection models. We demonstrate that a single dose of anti-CD40 alone can effectively convert CTL exhaustion by activating the mTORC1 pathway, leading to CTL proliferation, up-regulation of an effector-cytokine IFN-γ and the cytolytic effect in AdVova-B6 mice. Using anti-CD4 antibody and diphtheria toxin (DT) to deplete CD4T-cells and dendritic cells (DCs), we discovered that the CD40 agonist-induced conversion in AdVova-B6 and AdVova-CD11c-DTR mice is dependent upon host CD4T-cell and DC involvements. Moreover, CD40 agonist significantly enhances PD-1 antagonist effectiveness in rescuing exhausted CTLs in chronic infection. Taken together, our data demonstrate the importance of CD40 signaling in the conversion of CTL exhaustion and its ability to enhance PD-1 antagonist action in rescuing exhausted CTLs in chronic infection. Therefore, our findings may positively impact the design of new therapeutic strategies for chronic infectious diseases.
1275 related Products with: CD40 agonist converting CTL exhaustion via the activation of the mTORC1 pathway enhances PD-1 antagonist action in rescuing exhausted CTLs in chronic infection.Goat Anti-Human CTLA + CT anti H inh human blood an INK-128 Mechanisms: mTORC Pp-242 Mechanisms: mTORC1 Signal transduction antib AKT Phospho-Specific Arra AMPK Signaling Phospho-Sp Cancer Apoptosis Phospho- Chromatin Transcription P CREB Phospho-Specific Arr Cytoskeleton II Phospho-S GPCR Signaling to MAPK ER
#28082401 // Save this To Up
A Multifunctional Role for Adjuvant Anti-4-1BB Therapy in Augmenting Antitumor Response by Chimeric Antigen Receptor T Cells.Adoptive immunotherapy utilizing chimeric antigen receptor (CAR) T cells has demonstrated high success rates in hematologic cancers, but results against solid malignancies have been limited to date, due in part to the immunosuppressive tumor microenvironment. Activation of the 4-1BB (CD137) pathway using an agonistic α-4-1BB antibody is known to provide strong costimulatory signals for augmenting and diversifying T-cell responses. We therefore hypothesized that a combination of α-4-1BB and CAR T-cell therapy would result in improved antitumor responses. Using a human-Her2 self-antigen mouse model, we report here that α-4-1BB significantly enhanced CAR T-cell efficacy directed against the Her2 antigen in two different established solid tumor settings. Treatment also increased the expression of IFNγ and the proliferation marker Ki67 in tumor-infiltrating CAR T cells when combined with α-4-1BB. Strikingly, α-4-1BB significantly reduced host immunosuppressive cells at the tumor site, including regulatory T cells and myeloid-derived suppressor cells, correlating with an increased therapeutic response. We conclude that α-4-1BB has a multifunctional role for enhancing CAR T-cell responses and that this combination therapy has high translational potential, given current phase I/II clinical trials with α-4-1BB against various types of cancer..
1975 related Products with: A Multifunctional Role for Adjuvant Anti-4-1BB Therapy in Augmenting Antitumor Response by Chimeric Antigen Receptor T Cells.anti Transferrin receptor MOUSE ANTI BORRELIA BURGD Anti beta3 AR Human, Poly anti CD38 Hematopoietic p Goat Anti- Glucogon recep Goat Anti- TACR2 Neurokin Mouse Anti Progesterone R Mouse Anti Progesterone R Mouse Anti Progesterone R Mouse Anti Progesterone R Mouse Anti Progesterone R Mouse Anti P. aeruginosa
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45 Fax 0032 16 50 90 45
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50 Fax 01 43 25 01 60
52062 Aachen Deutschland
Tel 0241 40 08 90 86 Fax 0241 55 91 05 36
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
Schweiz Züri +41435006251
Česká republika Praha +420246019719
Ireland Dublin +35316526556
Norge Oslo +4721031366
Finland Helsset +358942419041
Sverige Stockholm +46852503438
Ελλάς Αθήνα +302111768494
Magyarország Budapest +3619980547
GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
Tel 058 710 33 44
Fax 058 710 33 48
GENTAUR Nederland BV
5521 DG Eersel Nederland
Tel 0208-080893 Fax 0497-517897
Piazza Giacomo Matteotti, 6, 24122 Bergamo
Tel 02 36 00 65 93 Fax 02 36 00 65 94
53 Iskar Str. 1191 Kokalyane, Sofia