Penn researchers discover potential cause of immunotherapy-related neurotoxicity

(University of Pennsylvania School of Medicine) New research has uncovered the previously unknown presence of CD19 -- a B cell molecule targeted by chimeric antigen receptor (CAR) T cell immunotherapy to treat leukemia, lymphoma, and multiple myeloma -- in brain cells that protect the blood brain barrier (BBB). This discovery may potentially be the cause for neurotoxicity in patients undergoing CD19 directed CAR T cell immunotherapy, according to the research team led by Avery Posey, PhD, an assistant professor of Systems Pharmacology and Translational Therapeutics at the University of Pennsylvania.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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ssi D Abstract Long non-coding RNAs (lncRNAs) play critical roles in various biological functions and disease processes including cancer. The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was initially identified as a lncRNA with elevated expression in primary human non-small cell lung tumors with high propensity to metastasize, and subsequently shown to be highly expressed in numerous other human cancers including breast, ovarian, prostate, cervical, endometrial, gastric, pancreatic, sarcoma, colorectal, bladder, brain, multiple myeloma, and lymphoma. MALAT1 is deeply involved in several physiol...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
CONCLUSIONS: Although our meta-analysis showed statistically significant increased risks of either cancer incidence or mortality of certain cancers in association with firefighting, a number of important limitations of the underlying studies exist, which, precluded our ability to arrive at definitive conclusions regarding causation. PMID: 31759344 [PubMed - in process]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation....
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion and Future Perspectives This review illustrates our current knowledge of USP7, including its source and characterization, structure, binding partners and substrates in various biological processes. Besides, how USP7 regulates various aspects of a cell under both normal and pathological states are elaborated in detail. As the processes of ubiquitination and deubiquitination are extremely dynamic and context-specific, a series of studies have linked USP7 to different cancers. The biology, particularly the immune oncology mechanisms, reveal that USP7 inhibitors would be useful drugs, thus it is vital to develop hi...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, CAR-T treatment combined with intratumoral delivery of poly I:C resulted in synergistic antitumor activity. We thus provide a rationale to translate this immunotherapeutic strategy to solid tumors. Introduction Adoptive T cell immunotherapy has been demonstrated to be a new way to fight malignancies. In particular, T lymphocytes engineered to express chimeric antigen receptor (CAR) have shown great promise in treating hematological malignancies (1). CD19-targeted CAR-T cells have been approved by FDA to treat relapsed B cell acute lymphoblastic leukemia (B-ALL) and Diffuse Large B-cell lymphoma (DLBC...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions: CAR T cell therapies have demonstrated the clinical benefits of harnessing our body's own defenses to combat tumor cells. Similar research is being conducted on lesser known modifications and gene-modified immune cells, which we highlight in this review. Introduction Chimeric antigen receptors and engineered T cell receptors (based on previously identified high affinity T cell receptors) function by redirecting T cells to a predefined tumor-specific (or tumor-associated) target. Most of these modifications use retroviral or lentiviral vectors to integrate the construct, and most of the receptors ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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