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T cell cancer therapy

Tianqun Lang, Yiran Liu, Zhong Zheng, Wei Ran, Yihui Zhai, Qi Yin, Pengcheng Zhang, Yaping Li
Metastatic breast cancer may be resistant to chemo-immunotherapy due to the existence of cancer stem cells (CSC). And the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti-CSC agent thioridazine (THZ), and the PD-1/PD-L1 inhibitor HY19991 (HY) are all incorporated into an enzyme/pH dual-sensitive nanoparticle with a micelle-liposome double-layer structure...
December 5, 2018: Advanced Materials
Viswanath Gunda, Benjamin Gigliotti, Tameem Ashry, Dorothy Ndishabandi, Michael McCarthy, Zhiheng Zhou, Salma Amin, Kyu Eun Lee, Tabea Stork, Lori Wirth, Gordon J Freeman, Alessandro Alessandrini, Sareh Parangi
Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite multimodal therapy with surgery and chemoradiation. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, and checkpoint inhibitors targeting the programmed cell death pathway have proven effective in some patients with advanced thyroid cancer. Combination of these therapies is a potential means to boost effectiveness and minimize treatment resistance in ATC. We utilized our novel immunocompetent murine model of orthotopic ATC to demonstrate that lenvatinib led to significant tumor shrinkage and increased survival, while combination therapy led to dramatic improvements in both...
December 4, 2018: International Journal of Cancer. Journal International du Cancer
Raphael Sexauer, Thomas Weikert, Kevin Mader, Andreas Wicki, Sabine Schädelin, Bram Stieltjes, Jens Bremerich, Gregor Sommer, Alexander W Sauter
Results of PET/CT examinations are communicated as text-based reports which are frequently not fully structured. Incomplete or missing staging information can be a significant source of staging and treatment errors. We compared standard text-based reports to a manual full 3D-segmentation-based approach with respect to TNM completeness and processing time. TNM information was extracted retrospectively from 395 reports. Moreover, the RIS time stamps of these reports were analyzed. 2995 lesions using a set of 41 classification labels (TNM features + location) were manually segmented on the corresponding image data...
2018: Contrast Media & Molecular Imaging
Guoliang Qiao, Xiao-Li Wang, Lei Zhou, Xin-Na Zhou, Yuguang Song, Shuo Wang, Lei Zhao, Michael A Morse, Amy Hobeika, Jin Song, Xin Yi, Xuefeng Xia, Jun Ren, Herbert Kim Lyerly
PURPOSE: We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer(AGC) and the role of mutational analysis of circulating tumor DNA(ctDNA) and T cell receptor (TCR) repertoire in predicting clinical outcomes. EXPERIMENTAL DESIGN: Consecutive patients (n=63) with advanced gastric cancer were allocated to treatment with S-1 alone, S-1 plus cisplatin, DC-CIK combined with S-1 or DC-CIK combined with S-1 plus cisplatin...
December 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Prithy C Martis, Atira T Dudley, Melissa A Bemrose, Hunter L Gazda, Barry H Smith, Lawrence S Gazda
BACKGROUND: Agarose encapsulated murine renal adenocarcinoma cells (RENCA macrobeads) are currently being investigated in clinical trials as a treatment for therapy-resistant metastatic colorectal cancer. We have previously demonstrated the capacity of RENCA macrobeads to produce diffusible substances that markedly inhibit the proliferation of epithelial-derived tumor cells outside the macrobead environment. This study examined the molecular mechanisms underlying the observed inhibition in targeted tumor cells exposed to RENCA macrobeads...
December 4, 2018: BMC Cancer
Kevin Sek, Christina Mølck, Gregory D Stewart, Lev Kats, Phillip K Darcy, Paul A Beavis
The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of 'checkpoint blockade' and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient's own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function...
December 2, 2018: International Journal of Molecular Sciences
Christopher T Lucido, W Keith Miskimins, Paola D Vermeer
Tumor cell metabolism differs from that of normal cells, conferring tumors with metabolic advantages but affording opportunities for therapeutic intervention. Accordingly, metabolism-targeting therapies have shown promise. However, drugs targeting singular metabolic pathways display limited efficacy, in part due to the tumor's ability to compensate by using other metabolic pathways to meet energy and growth demands. Thus, it is critical to identify novel combinations of metabolism-targeting drugs to improve therapeutic efficacy in the face of compensatory cellular response mechanisms...
November 30, 2018: Cancers
Mayassa J Bou-Dargham, Yuhang Liu, Qing-Xiang Amy Sang, Jinfeng Zhang
In the era of immunotherapy and personalized medicine, there is an urgent need for advancing the knowledge of immune evasion in different cancer types and identifying reliable biomarkers that guide both therapy selection and patient inclusion in clinical trials. Given the differential immune responses and evasion mechanisms in breast cancer, we expect to identify different breast cancer groups based on their expression of immune-related genes. For that, we used the sequential biclustering method on The Cancer Genome Atlas RNA-seq breast cancer data and identified 7 clusters...
2018: PloS One
Sanam Sadreddini, Behzad Baradaran, Ali Aghebati-Maleki, Sevil Sadreddini, Dariush Shanehbandi, Ali Fotouhi, Leili Aghebati-Maleki
Among the main promising systems to triggering therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoint pathways regulate the control and eradication of infections, malignancies, and resistance against a host of autoantigens. Initiation point of the immune response is T cells, which have a critical role in this pathway. As several immune checkpoints are initiated by ligand-receptor interactions, they can be freely blocked by antibodies or modulated by recombinant forms of ligands or receptors...
December 3, 2018: Journal of Cellular Physiology
Xuyan Liu, Mingzi Yang, Meng Wu, Wen Zheng, Yan Xie, Jun Zhu, Yuqin Song, Weiping Liu
PURPOSE: The standard treatment for peripheral T-cell lymphomas (PTCLs) is undetermined. We designed a CHOPE/G regimen (cyclophosphamide, pirarubicin, vincristine, prednisolone, and etoposide alternating with a gemcitabine-based regimen) as the first-line treatment of PTCLs and compared with CHOP (cyclophosphamide, pirarubicin, vincristine, and prednisolone) and CHOPE (CHOP plus etoposide) regimen to evaluate the optimal chemotherapy regimen. METHODS: 116 previously untreated PTCL patients received CHOP (N = 46), CHOPE (N = 46), or CHOPE/G (N = 24) regimen at Peking University Cancer Hospital from 2009 to 2017 and were retrospectively analyzed...
December 3, 2018: Cancer Chemotherapy and Pharmacology
Weihua Hou, Qingyun Yuan, Xingxing Yuan, Yuxiong Wang, Wei Mo, Huijie Wang, Min Yu
Background Redirecting T cells to tumor cells using bispecific antibodies (BsAbs) is emerging as a potent cancer therapy. The main concept of this strategy is to cross-link tumor cells and T cells by simultaneously binding to cell surface tumor-associated antigen (TAA) and the CD3ƹ chain. However, immune checkpoint programmed cell death ligand-1 (PD-L1) on tumor cells or other myeloid cells upreglulated remarkablely after the treatment of CD3-binding BsAbs, leads to the generation of suppressed microenvironment for immune evasion and tumor progression...
December 4, 2018: Investigational New Drugs
Zachary M Connelly, Shu Yang, Fenghua Chen, Yunshin Yeh, Nazih Khater, Renjie Jin, Robert Matusik, Xiuping Yu
Prostate cancer (PCa) is the leading cancer among men. Androgen Deprivation Therapy (ADT) is a common treatment for advanced PCa. However, ADT eventually fails and PCa relapses, developing into castration-resistant prostate cancer (CRPCa). Although alternative pathways such as cancer stem-cell pathway and neuroendocrine differentiation bypass androgen receptor (AR) signaling, AR remains the central player in mediating CRPCa. In this study, we identified a mechanism that retains AR signaling after androgen deprivation...
2018: American Journal of Clinical and Experimental Urology
Yuhui Wu, Junlin Yao, Jiansheng Xie, Zhen Liu, Yubin Zhou, Hongming Pan, Weidong Han
Autophagy is an evolutionarily conserved catabolic process that eliminates harmful components through lysosomal degradation. In addition to its role in maintaining cellular homeostasis, autophagy is critical to pathological processes, such as inflammation and cancer. Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer that develops from long-standing colitis in inflammatory bowel disease (IBD) patients. Accumulating evidence indicates that autophagy of microenvironmental cells plays different but vital roles during tumorigenesis and CAC development...
2018: Signal Transduction and Targeted Therapy
John P Murad, Anna K Kozlowska, Hee Jun Lee, Maya Ramamurthy, Wen-Chung Chang, Paul Yazaki, David Colcher, John Shively, Mihaela Cristea, Stephen J Forman, Saul J Priceman
Impressive clinical efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy for hematological malignancies have prompted significant efforts in achieving similar responses in solid tumors. The lack of truly restricted and uniform expression of tumor-associated antigens, as well as limited T cell persistence and/or tumor trafficking pose major challenges for successful translation of CAR T cell therapy in solid tumors. Recent studies have demonstrated that aberrantly glycosylated cell surface proteins on tumor cells are amenable CAR targets...
2018: Frontiers in Immunology
B Malicherova, T Burjanivova, E Minarikova, I Kasubova, T Pecova, M Bobrovska, I Homola, Z Lasabova, L Plank
Malignant melanoma is an oncological disease characterized by etiologic heterogeneity and it has increasing incidence and mortality in the Slovak Republic. While it is treated surgically in combination with chemotherapy, targeted therapy, and immunotherapy, malignant melanomas can ulcerate and are susceptible to infections. These are highly aggressive cancers with metastasis, and recent studies have shown the presence of mutations in RAC1, PPP6C and STK19 genes in melanoma patients. Mutations in these genes are driver mutations; important in oncogenesis and providing selective advantage to tumor cells...
August 9, 2018: Neoplasma
Xiaomeng Hu, Tingting Wu, Xianya Qin, Yan Qi, Qi Qiao, Conglian Yang, Zhiping Zhang
Cancer vaccines have shown great potential for treating different types of cancer. However, the application of vaccination still presents two major challenges. One is efficiency of antigen delivery, and the other is dealing with immune tolerance accompanied with tumor development. Lipid zinc phosphate hybrid nanoparticles (LZnP NPs) with a unique material structure can realize efficient delivery of antigens to dendritic cells (DCs) and also serve as an adjuvant to promote immune responses. Herein, ZnP NPs are introduced to load toll-like receptor 4 agonist (monophosphoryl lipid A) and B16F10 melanoma cell-derived tumor lysate (TLS) for vaccination...
December 3, 2018: Advanced Healthcare Materials
Matthew Evans, Brendan O'Sullivan, Matthew Smith, Philippe Taniere
The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Nevertheless, it is essential that testing laboratories are able to fulfil licencing criteria by providing the tests which have been validated as providing useful predictive information. Programmed cell death protein 1 (PD-1) expression assessment is now established in routine practice, although the situation regarding the selection of a particular assay remains complex, and testing protocols are likely to change in future...
December 2018: Translational Lung Cancer Research
Lizza E Hendriks, Etienne Rouleau, Benjamin Besse
Anti-programmed death (ligand)-1 [anti-PD-(L)1] therapies such as pembrolizumab, nivolumab or atezolizumab have become standard of care for non-small cell lung cancer (NSCLC) patients either in first line or beyond. PD-L1 expression level allows enriching the treated population with responders, but it is still not an optimal biomarker. Even in patients with PD-L1 tumor proportion score (TPS) levels of ≥50% treated with first line pembrolizumab overall response rate (ORR) is only 44.8% and overall survival at one year is 70%...
December 2018: Translational Lung Cancer Research
Ophir Vermesh, Amin Aalipour, T Jessie Ge, Yamil Saenz, Yue Guo, Israt S Alam, Seung-Min Park, Charlie N Adelson, Yoshiaki Mitsutake, Jose Vilches-Moure, Elias Godoy, Michael H Bachmann, Chin Chun Ooi, Jennifer K Lyons, Kerstin Mueller, Hamed Arami, Alfredo Green, Edward I Solomon, Shan X Wang, Sanjiv S Gambhir
The detection and analysis of rare blood biomarkers is necessary for early diagnosis of cancer and to facilitate the development of tailored therapies. However, current methods for the isolation of circulating tumour cells (CTCs) or nucleic acids present in a standard clinical sample of only 5-10 ml of blood provide inadequate yields for early cancer detection and comprehensive molecular profiling. Here, we report the development of a flexible magnetic wire that can retrieve rare biomarkers from the subject's blood in vivo at a much higher yield...
September 2018: Nature Biomedical Engineering
Anna E Oja, Berber Piet, David van der Zwan, Hans Blaauwgeers, Mark Mensink, Sander de Kivit, Jannie Borst, Martijn A Nolte, René A W van Lier, Regina Stark, Pleun Hombrink
Resident memory T cells (TRM ) inhabit peripheral tissues and are critical for protection against localized infections. Recently, it has become evident that CD103+ TRM are not only important in combating secondary infections, but also for the elimination of tumor cells. In several solid cancers, intratumoral CD103+ CD8+ tumor infiltrating lymphocytes (TILs), with TRM properties, are a positive prognostic marker. To better understand the role of TRM in tumors, we performed a detailed characterization of CD8+ and CD4+ TIL phenotype and functional properties in non-small cell lung cancer (NSCLC)...
2018: Frontiers in Immunology
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