scholarly journals 4-1BB (CD137) in anticancer chimeras

2020 ◽  
Vol 217 (12) ◽  
Author(s):  
Ignacio Melero ◽  
Pedro Berraondo
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Cytotoxic T Lymphocytes ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Costimulatory Signals

4-1BB (CD137, TNFRSF9) mediates costimulatory signals important for activation and persistence of cytotoxic T lymphocytes. In this issue of JEM, Oda et al. (https://doi.org/10.1084/jem.20191166) report on a chimeric construction encompassing extracellular Fas and intracellular 4-1BB to dramatically improve adoptive T cell therapy.

scholarly journals Cancer immunotherapy: current opportunities and perspectives

2021 ◽  
Vol 4 (2) ◽  
pp. 25-38
Author(s):  
O.Yu. Nikolaeva ◽  
R.V. Liubota ◽  
O.S. Zotov ◽  
R.I. Vereshchako
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Cancer Immunotherapy ◽  
Anticancer Agents ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
Tumor Focus

Cancer immunotherapy is a relatively new and pro­mising method of treating neoplasms. Understanding the antigen-directed cytotoxicity of T-lymphocytes has become one of the central directions in involving the immune system in the fight against cancer. Basic research in this area has led to the invention of checkpoint inhibitors, adoptive T-cell therapy, and cancer vaccines. Cytokines can enhance the action of T-lymphocytes for their ability to directly stimulate effector and stromal cells in tumor focus and enhance recognition of tumor cells by cytotoxic effector cells. They were the first in cancer immunotherapy and remain relevant to this day. Today, immunotherapy is an effective treatment for most malignant tumors, including melanoma, non-small cell lung cancer, liver, stomach, bladder, cervical cancer, some types of breast cancer, lymphoma, etc. However, immunotherapy of some malignant tumors is ineffective, therefore, the development of new and improvement of existing immunotherapy agents is actively underway, and there is a hope that the indications for its use will expand. For this purpose, this review discusses the principles of action of various classes of immunotherapeutic anticancer agents, namely cytokines, immune checkpoint inhibitors, and adaptive T-cell therapy. The work highlights their indications, efficacy and toxicity from the use of each class of drugs, as well as the prospects for the development of immunotherapeutic anticancer drugs.

scholarly journals ID:4007 Immune-cell base for cancer therapy

2017 ◽  
Vol 4 (S) ◽  
pp. 10
Author(s):  
Van Thanh Ta ◽  
Thinh Huy Tran ◽  
Binh Thanh Nguyen ◽  
Linh Quy Nguyen ◽  
Hoai Quy Nguyen ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Immune Cell ◽  
Specific Antigen ◽  
Cell Receptor ◽  
Adoptive T Cell Therapy ◽  
Target Cells ◽  
T Cell Therapy ◽  
Mhc Molecules

The development of immune cell-based approaches for treatment of cancer has been actively investigated for many years. One strategy that has been demonstrated as an effective method for cancer treatment is adoptive T cell therapy. The principle of this method is using Cytotoxic T lymphocytes (CTL), a crucial component of the adaptive immune system that aids in the control of intracellular pathogens. Effector CTL have the capacity to promote the apoptotic death of specifically targeted cells, using a combination of granule (perforin/granzyme)-and receptor (Fas/tumor necrosis factor)-mediated mechanisms. CTL recognize specific antigen on target cells using an unique T-cell receptor (TCR) when they are presented by class I major histocompatibility (MHC) molecules. In this study, we demonstrated that T lymphocytes were activated and dramatically expanded by stimulation with anti-CD3/CD28 antibodies and culture in the present of IL-2, IL-15 and IL-21 cytokines. These T cells exhibited a predominantly activated phenotype as manifested by an increase in the percentage of cells expressing CD8 and generation of various cytokines such as IL-2, INFγ and TNFa. These findings indicate that stimulation by anti- CD3/CD28 generated effector CTL in adoptive T-cell therapy for cancer.

scholarly journals T cell therapy with EBV-specific cytotoxic T-lymphocytes for patients with nasopharyngeal carcinoma

2018 ◽  
Vol 29 ◽  
pp. x11 ◽  
Author(s):  
P. Pedrazzoli ◽  
P. Comoli ◽  
S. Secondino ◽  
A. Gurrado ◽  
A. Pagani ◽  
...  
Keyword(s):  
T Cell ◽  
Nasopharyngeal Carcinoma ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Cytotoxic T Lymphocytes ◽  
T Cell Therapy

Genetic engineering of cytolytic T lymphocytes for adoptive T-cell therapy of neuroblastoma

2004 ◽  
Vol 6 (6) ◽  
pp. 704-711 ◽  
Author(s):  
Sergio Gonzalez ◽  
Araceli Naranjo ◽  
Lisa M. Serrano ◽  
Wen-Chung Chang ◽  
Christine L. Wright ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Genetic Engineering ◽  
Cell Therapy ◽  
Adoptive T Cell Therapy ◽  
Cytolytic T Lymphocytes ◽  
T Cell Therapy

scholarly journals Direct Toll-Like Receptor 8 signaling increases the functional avidity of human CD8+ T lymphocytes generated for adoptive T cell therapy strategies

2015 ◽  
Vol 3 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Jean-François Chatillon ◽  
Mohamad Hamieh ◽  
Florence Bayeux ◽  
Claire Abasq ◽  
Emilie Fauquembergue ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Therapy ◽  
Adoptive T Cell Therapy ◽  
Toll Like Receptor ◽  
Functional Avidity ◽  
T Cell Therapy ◽  
Cd8 T Lymphocytes ◽  
Therapy Strategies

scholarly journals 'Off-the-shelf’ allogeneic antigen-specific adoptive T-cell therapy for the treatment of multiple EBV-associated malignancies

2021 ◽  
Vol 9 (2) ◽  
pp. e001608
Author(s):  
Debottam Sinha ◽  
Sriganesh Srihari ◽  
Kirrliee Beckett ◽  
Laetitia Le Texier ◽  
Matthew Solomon ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Adoptive T Cell Therapy ◽  
Nuclear Antigen ◽  
T Cell Therapy ◽  
In Vivo Models ◽  
Hla Alleles ◽  
Cell Therapies ◽  
Wide Range

BackgroundEpstein-Barr virus (EBV), an oncogenic human gammaherpesvirus, is associated with a wide range of human malignancies of epithelial and B-cell origin. Recent studies have demonstrated promising safety and clinical efficacy of allogeneic ‘off-the-shelf’ virus-specific T-cell therapies for post-transplant viral complications.MethodsTaking a clue from these studies, we developed a highly efficient EBV-specific T-cell expansion process using a replication-deficient AdE1-LMPpoly vector that specifically targets EBV-encoded nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2), expressed in latency II malignancies.ResultsThese allogeneic EBV-specific T cells efficiently recognized human leukocyte antigen (HLA)-matched EBNA1-expressing and/or LMP1 and LMP2-expressing malignant cells and demonstrated therapeutic potential in a number of in vivo models, including EBV lymphomas that emerged spontaneously in humanized mice following EBV infection. Interestingly, we were able to override resistance to T-cell therapy in vivo using a ‘restriction-switching’ approach, through sequential infusion of two different allogeneic T-cell therapies restricted through different HLA alleles. Furthermore, we have shown that inhibition of the programmed cell death protein-1/programmed death-ligand 1 axis in combination with EBV-specific T-cell therapy significantly improved overall survival of tumor-bearing mice when compared with monotherapy.ConclusionThese findings suggest that restriction switching by sequential infusion of allogeneic T-cell therapies that target EBV through distinct HLA alleles may improve clinical response.

scholarly journals A modular and controllable T cell therapy platform for acute myeloid leukemia

Leukemia ◽  
2021 ◽  
Author(s):  
Mohamed-Reda Benmebarek ◽  
Bruno L. Cadilha ◽  
Monika Herrmann ◽  
Stefanie Lesch ◽  
Saskia Schmitt ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Cell Therapy ◽  
Myeloid Leukemia ◽  
Tumor Antigens ◽  
Adoptive T Cell Therapy ◽  
Single Chain ◽  
T Cell Therapy ◽  
Acute Myeloid

AbstractTargeted T cell therapy is highly effective in disease settings where tumor antigens are uniformly expressed on malignant cells and where off-tumor on-target-associated toxicity is manageable. Although acute myeloid leukemia (AML) has in principle been shown to be a T cell-sensitive disease by the graft-versus-leukemia activity of allogeneic stem cell transplantation, T cell therapy has so far failed in this setting. This is largely due to the lack of target structures both sufficiently selective and uniformly expressed on AML, causing unacceptable myeloid cell toxicity. To address this, we developed a modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to AML. This platform combines synthetic agonistic receptor (SAR) -transduced T cells with AML-targeting tandem single chain variable fragment (scFv) constructs. Construct exchange allows SAR T cells to be redirected toward alternative targets, a process enabled by the short half-life and controllability of these antibody fragments. Combining SAR-transduced T cells with the scFv constructs resulted in selective killing of CD33+ and CD123+ AML cell lines, as well as of patient-derived AML blasts. Durable responses and persistence of SAR-transduced T cells could also be demonstrated in AML xenograft models. Together these results warrant further translation of this novel platform for AML treatment.

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