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Cancer Immunology, Immunotherapy: CII

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https://www.readbyqxmd.com/read/29335856/abscopal-effects-of-radiotherapy-and-combined-mrna-based-immunotherapy-in-a-syngeneic-ova-expressing-thymoma-mouse-model
#1
Lucas Basler, Aleksandra Kowalczyk, Regina Heidenreich, Mariola Fotin-Mleczek, Savas Tsitsekidis, Daniel Zips, Franziska Eckert, Stephan M Huber
BACKGROUND: Tumor metastasis and immune evasion present major challenges of cancer treatment. Radiotherapy can overcome immunosuppressive tumor microenvironments. Anecdotal reports suggest abscopal anti-tumor immune responses. This study assesses abscopal effects of radiotherapy in combination with mRNA-based cancer vaccination (RNActive®). METHODS: C57BL/6 mice were injected with ovalbumin-expressing thymoma cells into the right hind leg (primary tumor) and left flank (secondary tumor) with a delay of 4 days...
January 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29335855/t-cell-responses-to-tumor-how-dominant-assumptions-on-immune-activity-led-to-a-neglect-of-pathological-functions-and-how-evolutionary-considerations-can-help-identify-testable-hypotheses-for-improving-immunotherapy
#2
REVIEW
Marinos Kallikourdis
Cancer immunotherapy is based on the premise that activated, pro-inflammatory T cell responses to tumor will mostly combat tumor growth. Nowadays accepted as largely valid, this hypothesis has been formed as a result of extensive theoretical and experimental argumentation on the inherent function of the immune system and the nature of the immunological self, dating back to the foundations of immunology. These arguments have also been affected by how current working hypotheses were set by researchers, an issue that has been the focus of study by medical anthropologists...
January 15, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29332158/combined-sublethal-irradiation-and-agonist-anti-cd40-enhance-donor-t-cell-accumulation-and-control-of-autochthonous-murine-pancreatic-tumors
#3
Lindsay K Ward-Kavanagh, Kathleen M Kokolus, Timothy K Cooper, Aron E Lukacher, Todd D Schell
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells...
January 13, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29330557/linear-doggybone-dna-vaccine-induces-similar-immunological-responses-to-conventional-plasmid-dna-independently-of-immune-recognition-by-tlr9-in-a-pre-clinical-model
#4
Alex Allen, Chuan Wang, Lisa J Caproni, Gessa Sugiyarto, Elena Harden, Leon R Douglas, Patrick J Duriez, Kinga Karbowniczek, Jon Extance, Paul J Rothwell, Ifeayinwa Orefo, John P Tite, Freda K Stevenson, Christian H Ottensmeier, Natalia Savelyeva
Vaccination with DNA that encodes cancer antigens is a simple and convenient way to raise immunity against cancer and has already shown promise in the clinical setting. Conventional plasmid DNA is commonly used which together with the encoded antigen also includes bacterial immunostimulatory CpG motifs to target the DNA sensor Toll-like receptor 9. Recently DNA vaccines using doggybone DNA (dbDNA™), have been developed without the use of bacteria. The cell-free process relies on the use of Phi29 DNA polymerase to amplify the template followed by protelomerase TelN to complete individual closed linear DNA...
January 12, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29327110/the-role-of-interleukin-2-all-trans-retinoic-acid-and-natural-killer-cells-surveillance-mechanisms-in-anti-gd2-antibody-therapy-in-neuroblastoma
#5
Rosa Nguyen, Jim Houston, Wing K Chan, David Finkelstein, Michael A Dyer
Although anti-disialoganglioside (GD2) antibodies are successfully used for neuroblastoma therapy, a third of patients with neuroblastoma experience treatment failure or serious toxicity. Various strategies have been employed in the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell function, adoptive transfer of allogeneic NK cells to exploit immune surveillance, and retinoid-induced differentiation therapy...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29327109/a-novel-biologic-platform-elicits-profound-t-cell-costimulatory-activity-and-antitumor-immunity-in-mice
#6
Joseph M Ryan, Payal Mittal, Antoine Menoret, Julia Svedova, Jeffrey S Wasser, Adam J Adler, Anthony T Vella
Combination immunotherapies utilizing complementary modalities that target distinct tumor attributes or immunosuppressive mechanisms, or engage different arms of the antitumor immune response, can elicit greater therapeutic efficacy than the component monotherapies. Increasing the number of agents included in a therapeutic cocktail can further increase efficacy, however, this approach poses numerous challenges for clinical translation. Here, a novel platform to simplify combination immunotherapy by covalently linking immunotherapeutic agonists to the costimulatory receptors CD134 and CD137 into a single heterodimeric drug, "OrthomAb", is shown...
January 11, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29313073/correction-to-characterization-of-the-first-fully-human-anti-tem1-scfv-in-models-of-solid-tumor-imaging-and-immunotoxin-based-therapy
#7
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, Nathalie Scholler, George Coukos
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 (3D) 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...
January 8, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29299660/reduction-of-myeloid-derived-suppressor-cells-reinforces-the-anti-solid-tumor-effect-of-recipient-leukocyte-infusion-in-murine-neuroblastoma-bearing-allogeneic-bone-marrow-chimeras
#8
Isabelle Dierckx de Casterlé, Sabine Fevery, Omer Rutgeerts, Fariba Poosti, Sofie Struyf, Caroline Lenaerts, Mark Waer, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation is an emerging treatment option for solid tumors because of its capacity to elicit immune graft-versus-tumor effects. However, these are often limited and associated with GvHD. Adoptive recipient leukocyte infusion (RLI) was shown to enhance anti-tumor responses of allogeneic bone marrow transplantation in murine neuroblastoma (Neuro2A)-bearing chimeras. In contrast to the clinically used donor leukocyte infusion, the RLI anti-tumor effect-elicited by host-versus-graft lymphohematopoietic reactivity-does not cause GvHD; however, the tumor growth-inhibitory effect is incomplete, because overall survival is not prolonged...
January 3, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29299659/ex-vivo-expanded-nk-cells-from-blood-and-ascites-of-ovarian-cancer-patients-are-cytotoxic-against-autologous-primary-ovarian-cancer-cells
#9
Tina Nham, Sophie M Poznanski, Isabella Y Fan, Mira M Shenouda, Marianne V Chew, Amanda J Lee, Fatemeh Vahedi, Yalda Karimi, Martin Butcher, Dean A Lee, Hal Hirte, Ali A Ashkar
Ovarian cancer (OC) is the leading cause of gynecological cancer-related death in North America. Most ovarian cancer patients (OCPs) experience disease recurrence after first-line surgery and chemotherapy; thus, there is a need for novel second-line treatments to improve the prognosis of OC. Although peripheral blood-derived NK cells are known for their ability to spontaneously lyse tumour cells without prior sensitization, ascites-derived NK cells (ascites-NK cells) isolated from OCPs exhibit inhibitory phenotypes, impaired cytotoxicity and may play a pro-tumourigenic role in cancer progression...
January 3, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29289977/anti-pd-1-induced-high-grade-hepatitis-associated-with-corticosteroid-resistant-t-cells-a-case-report
#10
Helen M McGuire, Elena Shklovskaya, Jarem Edwards, Paul R Trevillian, Geoffrey W McCaughan, Patrick Bertolino, Catriona McKenzie, Ralph Gourlay, Stuart J Gallagher, Barbara Fazekas de St Groth, Peter Hersey
Effective treatment or prevention of immune side effects associated with checkpoint inhibitor therapy of cancer is an important goal in this new era of immunotherapy. Hepatitis due to immunotherapy with antibodies against PD-1 is uncommon and generally of low severity. We present an unusually severe case arising in a melanoma patient after more than 6 months uncomplicated treatment with anti-PD-1 in an adjuvant setting. The hepatitis rapidly developed resistance to high-dose steroids, requiring anti-thymocyte globulin (ATG) to achieve control...
December 30, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29270668/cytosolic-high-mobility-group-box-protein-1-hmgb1-and-or-pd-1-%C3%A2-tils-in-the-tumor-microenvironment-may-be-contributing-prognostic-biomarkers-for-patients-with-locally-advanced-rectal-cancer-who-have-undergone-neoadjuvant-chemoradiotherapy
#11
Chih-Yang Huang, Shu-Fen Chiang, Tao-Wei Ke, Tsung-Wei Chen, Yu-Ching Lan, Ying-Shu You, An-Cheng Shiau, William Tzu-Liang Chen, K S Clifford Chao
Rectal cancer, which comprises 30% of all colorectal cancer cases, is one of the most common forms of cancer in the world. Patients with locally advanced rectal cancer (LARC) are often treated with neoadjuvant chemoradiotherapy (neoCRT) followed by surgery. However, after neoCRT treatment, approximately one-third of the patients progress to local recurrence or distant metastasis. In these studies, we found that patients with tumors that exhibited cytosolic HMGB1(Cyto-HMGB1) translocation and/or the presence of PD-1+ tumor-infiltrating lymphocytes (TILs) before treatment had a better clinical outcome...
December 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29264698/splice-variants-of-human-natural-cytotoxicity-receptors-novel-innate-immune-checkpoints
#12
REVIEW
Avishai Shemesh, Michael Brusilovsky, Kiran Kundu, Aner Ottolenghi, Kerry S Campbell, Angel Porgador
The natural cytotoxicity receptors (NCRs; NKp30, NKp44, and NKp46) were first defined as activating receptors on human NK cells that are important in recognition of and response to tumors. A flurry of recent research, however, has revealed that differential splicing can occur during transcription of each of the NCR genes, resulting in some transcripts that encode receptor isoforms with inhibitory functions. These alternative transcripts can arise in certain tissue microenvironments and appear to be induced by cytokines...
December 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29264697/correction-to-clinical-and-immunologic-evaluation-of-three-metastatic-melanoma-patients-treated-with-autologous-melanoma-reactive-tcr-transduced-t-cells
#13
Tamson Moore, Courtney Regan Wagner, Gina M Scurti, Kelli A Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M Hellman, Nishant K Singh, Fernando A Huyke, Siao-Yi Wang, Kelly M Calabrese, Heather D Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M Eby, Patrick J Stiff, Brian D Evavold, Brian M Baker, I Caroline Le Poole, Boro Dropulic, Joseph I Clark, Michael I Nishimura
The authors would like to make the following corrections to the published article.
December 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29256156/il-6-and-il-10-are-associated-with-good-prognosis-in-early-stage-invasive-breast-cancer-patients
#14
Narmeen Ahmad, Aula Ammar, Sarah J Storr, Andrew R Green, Emad Rakha, Ian O Ellis, Stewart G Martin
Macrophage-associated cytokines play an important role in cancer metastasis; however, the functions of interleukins (IL) 6 and 10 in breast cancer (BC) progression and metastasis are not clear. In this study the roles of IL-6/IL-10 in regulating vascular invasion and their prognostic significance in BC are investigated. MDA-MB-231 and MCF-7 migration (± IL-6 or IL-10) was assessed by scratch wound assay. Cancer cell adhesion to IL-6/IL-10 stimulated blood and lymphatic endothelial cells (EC) was investigated...
December 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29248956/human-c-src-kinase-csk-overexpression-makes-t-cells-dummy
#15
Else Marit Inderberg, Nadia Mensali, Morten P Oksvold, Lars-Egil Fallang, Anne Fåne, Gjertrud Skorstad, Grethe-Elisabeth Stenvik, Cinzia Progida, Oddmund Bakke, Gunnar Kvalheim, June H Myklebust, Sébastien Wälchli
Adoptive cell therapy with T-cell receptor (TCR)-engineered T cells represents a powerful method to redirect the immune system against tumours. However, although TCR recognition is restricted to a specific peptide-MHC (pMHC) complex, increasing numbers of reports have shown cross-reactivity and off-target effects with severe consequences for the patients. This demands further development of strategies to validate TCR safety prior to clinical use. We reasoned that the desired TCR signalling depends on correct pMHC recognition on the outside and a restricted clustering on the inside of the cell...
December 16, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29243049/high-pd-l1-expression-indicates-poor-prognosis-of-hiv-infected-patients-with-non-small-cell-lung-cancer
#16
Yusuke Okuma, Tsunekazu Hishima, Jumpei Kashima, Sadamu Homma
BACKGROUND: The status of antitumor immunity represented by the expression of programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) and immune cell (IC) infiltration is unknown in HIV-infected patients with non-small cell lung cancer (NSCLC). METHODS: Fifteen HIV-infected patients with NSCLC were compared with 29 non-HIV-infected patients with NSCLC. Analysis of 13 propensity-score-matched patients in the two groups was also compared. The expression of PD-1/PD-L1 and tumor infiltration by CD4+, CD8+, and CD56+ immune cells were examined by immunohistochemistry; score of ≥ 2 was defined as positive...
December 14, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29218366/haploidentical-natural-killer-cells-induce-remissions-in-non-hodgkin-lymphoma-patients-with-low-levels-of-immune-suppressor-cells
#17
Veronika Bachanova, Dhifaf Sarhan, Todd E DeFor, Sarah Cooley, Angela Panoskaltsis-Mortari, Bruce R Blazar, Julie M Curtsinger, Linda Burns, Daniel J Weisdorf, Jeffrey S Miller
We report a novel phase 2 clinical trial in patients with poor prognosis refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical donor natural killer (NK) cell therapy (NK dose 0.5-3.27 × 107 NK cells/kg) with rituximab and IL-2 (clinicaltrials.gov NCT01181258). Therapy was tolerated without graft-versus-host disease, cytokine release syndrome, or neurotoxicity. Of 14 evaluable patients, 4 had objective responses (29%; 95% CI 12-55%) at 2 months: 2 had complete response lasting 3 and 9 months...
December 7, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29214427/characterization-of-pd-l1-expression-in-chinese-non-small-cell-lung-cancer-patients-with-pten-expression-as-a-means-for-tissue-quality-screening
#18
Xu-Chao Zhang, Xu Cao, Chun Sun, Zhi Xie, Jian-Jun Guo, Jin-Ji Yang, Xue-Ning Yang, Hang-Jun Dai, Su-Chun Li, Xin-Ran Xu, Yun-Xia Zuo, Meng Chen, Hartmut Koeppen, Jing He, Astrid Kiermaier, David Shames, Gang Cheng, Yi-Long Wu
The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay...
December 6, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29204702/post-treatment-neutrophil-to-lymphocyte-ratio-at-week-6-is-prognostic-in-patients-with-advanced-non-small-cell-lung-cancers-treated-with-anti-pd-1-antibody
#19
Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Miso Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo, Jong Seok Lee
We investigated inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) that may predict the response to anti-PD-1 (programmed cell death protein 1) antibody therapy. Data from 54 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1 antibodies were retrospectively analyzed. The NLR was assessed at baseline and 6 weeks after the start of treatment (post-treatment). Eighteen of 54 patients (33.3%) had objective responses to treatment. Older age, absence of brain metastasis, low post-treatment NLR (< 5), and immune-related adverse events were significantly associated with response...
December 4, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29204701/combination-of-mab-ar20-5-anti-pd-l1-and-polyiclc-inhibits-tumor-progression-and-prolongs-survival-of-muc1-tg-mice-challenged-with-pancreatic-tumors
#20
Kamiya Mehla, Jarrod Tremayne, James A Grunkemeyer, Kelly A O'Connell, Maria M Steele, Thomas C Caffrey, Xinyi Zhu, Fang Yu, Pankaj K Singh, Birgit C Schultes, Ragupathy Madiyalakan, Christopher F Nicodemus, Michael A Hollingsworth
A substantial body of evidence suggests the existence of MUC1-specific antibodies and cytotoxic T cell activities in pancreatic cancer patients. However, tumor-induced immunosuppression renders these responses ineffective. The current study explores a novel therapeutic combination wherein tumor-bearing hosts can be immunologically primed with their own antigen, through opsonization with a tumor antigen-targeted antibody, mAb-AR20.5. We evaluated the efficacy of immunization with this antibody in combination with PolyICLC and anti-PD-L1...
December 4, 2017: Cancer Immunology, Immunotherapy: CII
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