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Cancer Immunology, Immunotherapy: CII

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https://www.readbyqxmd.com/read/27933426/characterization-of-the-first-fully-human-anti-tem1-scfv-in-models-of-solid-tumor-imaging-and-immunotoxin-based-therapy
#1
Xiaopeng Yuan, Mingjuan Yang, Xiang Chen, Xuhua Zhang, Shrey Sukhadia, Najia Musolino, Huijing Bao, Tingtao Chen, Chen Xu, Qirui Wang, Stephen Santoro, Daniel Ricklin, Jia Hu, Ruihe Lin, Wei Yang, Zhijun Li, Weijun Qin, Aizhi Zhao
Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. We previously isolated a novel single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library. Here, we evaluated the potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. Epitope mapping, three-dimensional structure docking and affinity measurements indicated that scFv78 could bind to both human and murine TEM1, with equivalent affinity, at a well-conserved conformational epitope...
December 8, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27915371/histone-deacetylase-inhibitors-deplete-myeloid-derived-suppressor-cells-induced-by-4t1-mammary-tumors-in-vivo-and-in-vitro
#2
Hai-Fang Wang, Fen Ning, Zong-Cai Liu, Long Wu, Zi-Qian Li, Yi-Fei Qi, Ge Zhang, Hong-Sheng Wang, Shao-Hui Cai, Jun Du
Myeloid-derived suppressor cells (MDSC) have been identified as a population of immature myeloid cells that suppress anti-tumor immunity. MDSC are increased in tumor-bearing hosts; thus, depletion of MDSC may enhance anti-tumor immunity. Histone deacetylase inhibitors (HDACi) are chemical agents that are primarily used against hematologic malignancies. The ability of these agents to modulate anticancer immunity has recently been extensively studied. However, the effect of HDACi on MDSC has remained largely unexplored...
December 3, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27915370/prognostic-significance-of-the-lymphocyte-to-monocyte-ratio-and-the-tumor-infiltrating-lymphocyte-to-tumor-associated-macrophage-ratio-in-patients-with-stage-t3n0m0-esophageal-squamous-cell-carcinoma
#3
Yingming Zhu, Minghuan Li, Cong Bo, Xuemei Liu, Jianbo Zhang, Zhenxiang Li, Fen Zhao, Li Kong, Jinming Yu
PURPOSE: We assessed the prognostic significance of, and the relationship between, the pretreatment lymphocyte-to-monocyte ratio (LMR) and the TILs/tumor-associated macrophages (TAMs) ratio, in patients with esophageal squamous cell carcinoma (ESCC) of pathological stage T3N0M0 (pT3N0M0). METHODS: A total of 220 newly diagnosed ESCC patients of stage pT3N0M0 who had not undergone neoadjuvant therapy were included. Densities of CD8+ TILs, CD4+ TILs, CD45RO+ TILs, and CD68+ TAMs were assessed by immunohistochemical staining of tissue microarray cores from all 220 pT3N0M0 ESCC patients (who underwent radical resection)...
December 3, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27913835/preventive-dna-vaccination-against-cea-expressing-tumors-with-anti-idiotypic-scfv6-c4-dna-in-cea-expressing-transgenic-mice
#4
Priscila M A Denapoli, Bianca F Zanetti, Adara A Dos Santos, Jane Z de Moraes, Sang W Han
Carcinoembryonic antigen (CEA) is expressed during embryonic life and in low level during adult life. Consequently, the CEA is recognized by the immune system as a self-antigen and thus CEA-expressing tumors are tolerated. Previously, we constructed a single chain variable fragment using the 6.C4 (scFv6.C4) hybridoma cell line, which gave rise to antibodies able to recognize CEA when C57/Bl6 mice were immunized. Here, the scFv6.C4 ability to prevent the CEA-expressing tumor growth was assessed in CEA-expressing transgenic mice CEA2682...
December 2, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27896368/targeting-of-the-wt191-138-fragment-to-human-dendritic-cells-improves-leukemia-specific-t-cell-responses-providing-an-alternative-approach-to-wt1-based-vaccination
#5
Nergui Dagvadorj, Anne Deuretzbacher, Daniela Weisenberger, Elke Baumeister, Johannes Trebing, Isabell Lang, Carolin Köchel, Markus Kapp, Kerstin Kapp, Andreas Beilhack, Thomas Hünig, Hermann Einsele, Harald Wajant, Götz Ulrich Grigoleit
Due to its immunogenicity and overexpression concomitant with leukemia progression, Wilms tumor protein 1 (WT1) is of particular interest for immunotherapy of AML relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, WT1-specific T-cell responses have mainly been induced by vaccination with peptides presented by certain HLA alleles. However, this approach is still not widely applicable in clinical practice due to common limitations of HLA restriction. Dendritic cell (DC) vaccines electroporated with mRNA encoding full-length protein have also been tested for generating WT1-derived peptides for presentation to T-cells...
November 28, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27889799/a-polymorphism-in-the-promoter-region-of-pd-l1-serves-as-a-binding-site-for-sp1-and-is-associated-with-pd-l1-overexpression-and-increased-occurrence-of-gastric-cancer
#6
Li-Hua Tao, Xin-Ru Zhou, Fu-Chao Li, Qi Chen, Fan-Yi Meng, Yong Mao, Rui Li, Dong Hua, Hong-Jian Zhang, Wei-Peng Wang, Wei-Chang Chen
PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes...
November 26, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27889798/selective-effect-of-cytokine-induced-killer-cells-on-survival-of-patients-with-early-stage-melanoma
#7
Hong Li, Lan Huang, Linbo Liu, Ximei Wang, Zhen Zhang, Dongli Yue, Wei He, Kun Fu, Xueli Guo, Jianmin Huang, Xuan Zhao, Yu Zhu, Liping Wang, Wenjie Dong, Yan Yan, Li Xu, Ming Gao, Shuangning Yang, Yi Zhang
Adoptive immunotherapy using cytokine-induced killer (CIK) cells has shown potential antitumor ability against several kinds of cancers, including melanoma. However, little is known about the achievable outcome of CIK cells in melanoma patients at different pathological stages. Here we recruited 55 patients treated with conventional therapy plus CIK cells as the CIK group, and 49 patients treated with conventional therapy alone as the control group. The pathological characteristics were comparable between two groups, with a follow-up period up to 40 months...
November 26, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27888293/cytokine-induced-killer-cells-hunt-individual-cancer-cells-in-droves-in-a-mouse-model
#8
Ji Sung Kim, Yong Guk Kim, Hong Kyung Lee, Eun Jae Park, Boyeong Kim, Jong Soon Kang, Heesoon Lee, Youngsoo Kim, Jin Tae Hong, Sang-Bae Han
Cytotoxicity of cytokine-induced killer (CIK) cells depends mainly on their encounters with target cells, but how many CIK cells are required to kill an individual cancer cell is unknown. Here we used time-lapse imaging to quantify the critical effector cell number required to kill an individual target cell. CIK cells killed MHC-I-negative and MHC-I-positive cancer cells, but natural killer (NK) cells destroyed MHC-I-negative cells only. The average threshold number of CIK cells required to kill an individual cancer cell was 6...
November 25, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27885383/schwann-cells-a-new-player-in-the-tumor-microenvironment
#9
REVIEW
Yuri L Bunimovich, Anton A Keskinov, Galina V Shurin, Michael R Shurin
Cancerous cells must cooperate with the surrounding stroma and non-malignant cells within the microenvironment to support the growth and invasion of the tumor. The nervous system is a component of every organ system of the body, and therefore, is invariably at the front line of the tumor invasion. Due to the complexity of the nervous system physiology, this review separately discusses the contributions of the central and peripheral nervous systems to the tumorigenesis and tumor progression. We further focus the discussion on the evidence that Schwann cells aid in tumor growth and invasion...
November 24, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27872951/immunogenicity-and-efficacy-of-a-rationally-designed-vaccine-against-vascular-endothelial-growth-factor-in-mouse-solid-tumor-models
#10
Aizhang Xu, Li Zhang, Yangyang Chen, Zhibing Lin, Rongxiu Li
Vascular endothelial growth factor (VEGF) plays an important role in the progression of various cancers. The VEGF-specific antibody bevacizumab combined with chemotherapy was shown to significantly improve progression-free survival in certain cancers. However, repeated administration is necessary for effective suppression of VEGF, thereby making the therapy expensive and cumbersome. Thus, it is urgent to develop alternative reagents such as VEGF vaccines. Here we report that DTT-VEGF, a VEGF-based antigen consisting of the receptor-binding domain of VEGF and diphtheria toxin T domain (DTT), not only stimulated neutralizing antibody response, but also induced type 1 immune response as well as anti-tumor cytotoxic T lymphocytes in mice when administered with aluminum hydroxide adjuvant...
November 21, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27866242/elevated-systemic-interleukin-7-in-patients-with-colorectal-cancer-and-individuals-at-high-risk-of-cancer-association-with-lymph-node-involvement-and-tumor-location-in-the-right-colon
#11
Malgorzata Krzystek-Korpacka, Marek Zawadzki, Katarzyna Neubauer, Iwona Bednarz-Misa, Sabina Górska, Jerzy Wiśniewski, Wojciech Witkiewicz, Andrzej Gamian
Interleukin (IL)-7 is a cytokine essential for protective immunity, and it is considered as a promising agent for cancer immunotherapy. Recent studies, however, appear to associate IL-7 with aggressiveness of solid tumors. The IL-7 has been less studied in colorectal cancer (CRC) and conditions associated with increased risk of CRC development. To explore IL-7 status in bowel diseases, it was measured immunofluorometrically in 431 individuals (110 with CRC) by using Luminex platform. A level of IL-7 in CRC patients was significantly higher than in controls, did not differ from those with adenomas, but was lower than in both active and inactive inflammatory bowel disease (IBD) cases...
November 19, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27866241/elevated-regulatory-t-cells-surface-and-intracellular-ctla-4-expression-and-interleukin-17-in-the-lung-cancer-microenvironment-in-humans
#12
Iwona Kwiecien, Anna Stelmaszczyk-Emmel, Malgorzata Polubiec-Kownacka, Dariusz Dziedzic, Joanna Domagala-Kulawik
Regulatory T cells (Tregs) play an important role in the suppression of the immune response in lung cancer. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) expressed on T lymphocytes is capable of downregulating cytotoxic T cells and is constitutively expressed on Tregs. Little is known about the population of Tregs with two forms of CTLA-4: surface (s) and intracellular (in) in the lung cancer environment. Th17 cells defined by production of IL-17 have pleiotropic functions in anticancer immune response. Our aim was to detect the elements of immune response regulation in lung cancer in three compartments: by analysis of bronchoalveolar lavage fluid (BALF) from the lung affected by cancer (clBALF), healthy symmetrical lung (hlBALF) and peripheral blood (PB) from the same patient...
November 19, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27864613/oncolysate-loaded-escherichia-coli-bacterial-ghosts-enhance-the-stimulatory-capacity-of-human-dendritic-cells
#13
Jaroslav Michalek, Renata Hezova, Pavlina Turanek-Knötigova, Jana Gabkova, Marius Strioga, Werner Lubitz, Pavol Kudela
The natural adjuvant properties of bacterial ghosts (BGs) lie within the presence of intact pathogen-associated molecular patterns on their surface. BGs can improve the direct delivery, natural processing and presentation of target antigens within dendritic cells (DCs). Moreover, sensitization of human DCs by cancer cell lysate (oncolysate)-loaded BGs in the presence of IFN-α and GM-CSF enhanced DC maturation as indicated by an increased expression of maturation markers and co-stimulatory molecules, higher production of IL-12p70 and stimulation of significantly increased proliferation of both autologous CD4(+) and CD8(+) T cells compared to DCs matured in the presence of purified lipopolysaccharide...
November 18, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27858102/interleukin-10-expression-is-related-to-aggressiveness-and-poor-prognosis-of-patients-with-thyroid-cancer
#14
Lucas Leite Cunha, Elaine Cristina Morari, Sueli Nonogaki, Marjory Alana Marcello, Fernando Augusto Soares, José Vassallo, Laura Sterian Ward
Most patients with thyroid cancer will evolve very well with current therapies. However, 10-30% of these patients will present recurrent disease and some of them will eventually die. IL-10 is an anti-inflammatory and immunosuppressive cytokine that can contribute to the immune escape of neoplastic cells. We aimed to investigate IL-10 as a molecular marker to improve the clinical management of patients with thyroid cancer. We retrospectively studied 162 patients with follicular cell-derived thyroid cancer who attended to our institution, including 63 classic papillary thyroid carcinomas, 46 follicular variant of papillary thyroid carcinomas, 11 poorly differentiated thyroid carcinomas and 42 follicular thyroid carcinomas...
November 17, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27858101/a-novel-three-dimensional-heterotypic-spheroid-model-for-the-assessment-of-the-activity-of-cancer-immunotherapy-agents
#15
Sylvia Herter, Laura Morra, Ramona Schlenker, Jitka Sulcova, Linda Fahrni, Inja Waldhauer, Steffi Lehmann, Timo Reisländer, Irina Agarkova, Jens M Kelm, Christian Klein, Pablo Umana, Marina Bacac
The complexity of the tumor microenvironment is difficult to mimic in vitro, particularly regarding tumor-host interactions. To enable better assessment of cancer immunotherapy agents in vitro, we developed a three-dimensional (3D) heterotypic spheroid model composed of tumor cells, fibroblasts, and immune cells. Drug targeting, efficient stimulation of immune cell infiltration, and specific elimination of tumor or fibroblast spheroid areas were demonstrated following treatment with a novel immunocytokine (interleukin-2 variant; IgG-IL2v) and tumor- or fibroblast-targeted T cell bispecific antibody (TCB)...
November 17, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27853827/increased-pd-l1-and-t-cell-infiltration-in-the-presence-of-hla-class-i-expression-in-metastatic-high-grade-osteosarcoma-a-rationale-for-t-cell-based-immunotherapy
#16
Yayan T Sundara, Marie Kostine, Arjen H G Cleven, Judith V M G Bovée, Marco W Schilham, Anne-Marie Cleton-Jansen
INTRODUCTION: Immunotherapy may be an excellent choice for treating osteosarcoma given its exceptionally high genomic instability, potentially generating neoantigens. In this study, we aim to investigate the HLA class I expression, PD-L1 and tumour-infiltrating lymphocytes in primary osteosarcomas and relapses/metastases, as well as their changes during disease progression. MATERIALS AND METHODS: Tumour samples from multiple stages of the disease (pretreatment biopsies, surgical resections of primary osteosarcomas, relapses and metastases) were collected and stained for HLA-A (HCA2), HLA-B/C (HC10), β2-microglobulin and PD-L1 using immunohistochemistry on whole sections...
November 16, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27838762/efficacy-and-toxicity-of-rechallenge-with-combination-immune-checkpoint-blockade-in-metastatic-melanoma-a-case-series
#17
Lavinia Spain, Gerard Walls, Christina Messiou, Samra Turajlic, Martin Gore, James Larkin
BACKGROUND: The efficacy and potential toxicity of rechallenge with combination ipilimumab and nivolumab has not been described. Retreatment of patients with immune checkpoint inhibitors in the setting of prior significant toxicity lacks evidence-based guidance. METHODS: We present the first three, consecutive patients who received re-treatment with combination ipilimumab and nivolumab for metastatic melanoma managed at our institution. RESULTS: Rechallenge with combination ipilimumab and nivolumab in the setting of prior grade 3 toxicity with initial combination therapy is feasible, and responses are seen...
November 12, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27832318/immunological-effects-of-a-novel-rna-based-adjuvant-in-liver-cancer-patients
#18
Luisa Circelli, Annacarmen Petrizzo, Maria Tagliamonte, Regina Heidenreich, Maria Lina Tornesello, Franco M Buonaguro, Luigi Buonaguro
Evaluation of biological effects of adjuvants on immune cells has been assessed in a limited number of studies. Moreover, no data are available on samples derived from cancer patients who may have a severe immune impairment. The effects of a novel RNA-based adjuvant (RNAdjuvant(®) developed by CureVac) were assessed in an ex vivo setting on PBMCs obtained from 8 healthy volunteers and 17 HCC patients, using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression, cytokine production as well as gene expression was performed...
November 10, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27815572/phase-i-ii-study-of-lenalidomide-and-alemtuzumab-in-refractory-chronic-lymphocytic-leukemia-cll-effects-on-t-cells-and-immune-checkpoints
#19
Maria Winqvist, Fariba Mozaffari, Marzia Palma, Sandra Eketorp Sylvan, Lotta Hansson, Håkan Mellstedt, Anders Österborg, Jeanette Lundin
This phase I-II study explored safety, immunomodulatory and clinical effects of lenalidomide (weeks 1-16) and alemtuzumab (weeks 5-16) in 23 patients with refractory chronic lymphocytic leukemia. Most patients had Rai stage III/IV disease and were heavily pretreated (median 4 prior therapies), and 61% had del(17p)/del(11q). Eleven of 19 evaluable patients (58%) responded, with a median response duration of 12 months (1-29+); time to progression was short in non-responders. Lenalidomide had a narrow therapeutic dose range, 2...
November 4, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27796477/neutrophils-from-chronic-lymphocytic-leukemia-patients-exhibit-an-increased-capacity-to-release-extracellular-traps-nets
#20
Enrique Podaza, Florencia Sabbione, Denise Risnik, Mercedes Borge, María B Almejún, Ana Colado, Horacio Fernández-Grecco, María Cabrejo, Raimundo F Bezares, Analía Trevani, Romina Gamberale, Mirta Giordano
Chronic lymphocytic leukemia (CLL) is characterized by immune defects that contribute to a high rate of infections and autoimmune cytopenias. Neutrophils are the first line of innate immunity and respond to pathogens through multiple mechanisms, including the release of neutrophil extracellular traps (NETs). These web-like structures composed of DNA, histones, and granular proteins are also produced under sterile conditions and play important roles in thrombosis and autoimmune disorders. Here we show that neutrophils from CLL patients are more prone to release NETs compared to those from age-matched healthy donors (HD)...
October 28, 2016: Cancer Immunology, Immunotherapy: CII
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