Discovery opens door to new strategy for cancer immunotherapy

Scientists raise the prospect of cancer therapy that works by converting a tumor's best friends in the immune system into its gravest enemies. The team has uncovered a mechanism that allows key immune system cells to keep a steady rein on their more belligerent brother cells, thereby protecting normal, healthy tissue from assault. The discovery has powerful implications for cancer immunotherapy, researchers say.
Source: ScienceDaily Headlines - Category: Science Source Type: news

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Abstract Glioblastoma (GBM) is a devastating disease with an extremely poor prognosis. Immune therapy via adoptive cell transfer (ACT), especially with T cells engineered to express chimeric antigen receptors (CARs), represents a particularly promising approach. Despite the recent success of CAR T cells for blood cancers, the question remains whether this powerful anti-cancer therapy will ultimately work for brain tumors, and if the primary immunologic challenges in this disease-which include antigenic heterogeneity, immune suppression and T-cell exhaustion-can be adequately addressed. Here, we contextualize these...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Conclusion: The ethanol ADH acetaldehyde system offers a simple, safe, non-toxic approach to cancer therapy prodrug toxin technology. It may also offer a safe and non-toxic system to control the number and action of T cells used in adoptive immunotherapy.
Source: Current Pharmacogenomics and Personalized Medicine - Category: Genetics & Stem Cells Source Type: research
Publication date: Available online 9 November 2018Source: Biochimica et Biophysica Acta (BBA) - Reviews on CancerAuthor(s): Dan Liu, Xiaoxi Li, Xintian Chen, Yu Sun, Anqun Tang, Zhongwei Li, Junnian Zheng, Ming ShiAbstractThe treatment of cancer has made great progress. However, drug resistance remains problematic. Multiple physiologic processes of tumor development can be dominated by central and sympathetic nervous systems. The interactions between the nervous system, immune system, and tumor occur consistently and dynamically. Recent evidence suggests that nerves and neural signals are intimately involved in the develop...
Source: Biochimica et Biophysica Acta (BBA) Reviews on Cancer - Category: Cancer & Oncology Source Type: research
Publication date: February 2019Source: Biomedical Signal Processing and Control, Volume 48Author(s): Francisco F. Teles, João M. LemosAbstractDuring the last years several clinical decision support systems have been developed, some of which clearly improved the results obtained with standard clinical practice. However, this kind of decision computing process has not been quite explored in cancer treatment. In this work a control system that designs an optimal therapy based on adaptive control methods, aiming to allow the eradication of a metastatic renal cell carcinoma as quickly and efficiently as possible, and wit...
Source: Biomedical Signal Processing and Control - Category: Biomedical Science Source Type: research
AbstractLimitations of immunotherapy include poorly functioning events early in the immune response cycle, such as efficient antigen presentation and T cell priming. CD40 signaling in dendritic cells leads to upregulation of cell surface costimulatory and MHC molecules and the generation of cytokines, which promotes effective priming of CD8+ effector T cells while minimizing T cell anergy and the generation of regulatory T cells. This naturally occurs through interaction with CD40 ligand (CD40L) expressed on CD4+ T-helper cells. CD40 signaling can also be achieved using specific antibodies, leading to several agonist CD40 ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
CONCLUSION: PD-1/PD-L1 inhibitors show significant anti-cancer responses as stand-alone agents and in combination with other cancer therapies. More efficient experimental studies and clinical trials are necessary to evaluate the host-tumor cells' interactions. Understanding the cancer microenvironment, identifying specific biomarkers and X-ray crystalline structures of PD-1/PD-L1 complexes, including molecular and genomic signature studies are essential to determine the feasibility of PD-1/PD-L1 inhibitors for development into drug-like cancer immunotherapeutics. PMID: 30370857 [PubMed - as supplied by publisher]
Source: Recent Patents on Anti-Cancer Drug Discovery - Category: Cancer & Oncology Tags: Recent Pat Anticancer Drug Discov Source Type: research
Abstract Significant progress has been made in cancer immunotherapy with checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)-programmed death-ligand 1 signaling pathways. Tumors from patients showing sustained treatment response predominately demonstrate a T cell-inflamed tumor microenvironment prior to, or early on treatment. Not all tumors with this phenotype respond however and one mediator of immunosuppression in T cell-inflamed tumors is the tryptophan-kynurenine-aryl hydrocarbon receptor (Trp-Kyn-AhR) pathway. Multiple mechanisms of immunosuppression may be mediated by this pathway includi...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
SummaryExpression of CD155 differs between tumor and normal tissues, and high expression of this molecule can promote tumor metastasis. Here, we investigate whether CD155 can serve as a target for T cell-mediated immunotherapy of human prostate cancer. We first demonstrate that prostate cancer cells, including PC-3, PC-3  M, and LNCAP cells, express CD155 at high levels. Next, the specific cytotoxic activity of activated T cells (ATCs) armed with a novel anti-CD3 × anti-CD155 bispecific antibody (CD155Bi-Ab) against tumor cells was evaluated by flow cytometry, lactate dehydrogenase assay (LDH), and ELI...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
Abstract Adoptive immunotherapy is a promising cancer treatment that entails infusion of immune cells manipulated to have antitumor specificity, in vitro. Antigen-specific cytotoxic T lymphocytes are the main executors of transformed cells during cancer immunotherapy. To induce antigen-specific cytotoxic T lymphocytes, we developed artificial antigen-presenting cells (aAPCs) by engineering K562 cells with electroporation to direct the stable expression of HLA-A∗0201, CD80, and 4-1BBL. Our findings demonstrate that after three stimulation cycles, the aAPCs promoted the induction of antigen-specific cytotoxic...
Source: Cellular Immunology - Category: Allergy & Immunology Authors: Tags: Cell Immunol Source Type: research
In this report, we propose that the molecular mechanisms of beneficial actions of CR should be classified and discussed according to whether they operate under rich or insufficient energy resource conditions. Future studies of the molecular mechanisms of the beneficial actions of CR should also consider the extent to which the signals/factors involved contribute to the anti-oxidative, anti-inflammatory, anti-tumor and other CR actions in each tissue or organ, and thereby lead to anti-aging and prolongevity. RNA Interference of ATP Synthase Subunits Slows Aging in Nematodes
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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