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Immunotherapy cancer

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https://www.readbyqxmd.com/read/29055013/a-synthetic-cd8%C3%AE-myd88-co-receptor-enhances-cd8-t-cell-responses-to-weakly-immunogenic-and-lowly-expressed-tumor-antigens
#1
Sabina Kaczanowska, Ann Mary Joseph, Jitao Guo, Alexander K Tsai, Jackline Joy M Lasola, Kenisha Younger, Yuji Zhang, Cruz Velasco Gonzalez, Eduardo Davila
T cell-based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T cell efficacy, including suboptimal T cell receptor (TCR) activation and an immunosuppressive tumor environment. Here we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8+ T cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88-engineered T cells exhibited increased proliferation and expression of effector and co-stimulatory molecules in a tumor antigen-dependent manner...
October 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/29054890/natural-killer-t-cell-immunotherapy-in-combination-with-chemotherapy-induced-immunogenic-cell-death-targets-metastatic-breast-cancer
#2
Simon Gebremeskel, Lynnea Lobert, Kaitlyn Tanner, Brynn Walker, Tora Oliphant, Livia E Clarke, Graham Dellaire, Brent Johnston
Natural killer T (NKT) cells are glycolipid-reactive lymphocytes that promote cancer control. In previous studies, NKT-cell activation improved survival and antitumor immunity in a post-surgical mouse model of metastatic breast cancer. Herein, we investigated whether NKT-cell activation could be combined with chemotherapeutic agents to augment therapeutic outcomes. Gemcitabine and cyclophosphamide analogs enhanced the potential immunogenicity of 4T1 mammary carcinoma cells by increasing the expression of antigen-presenting molecules (MHC-I, MHC-II, and CD1d) and promoting exposure or release of immunogenic cell death markers (calreticulin, HMGB1 and ATP)...
October 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29054544/-abnormalities-of-dna-repair-and-gynecological-cancers
#3
REVIEW
Aurélie Auguste, Alexandra Leary
The demonstration of frequent defects in the DNA damage response in high grade ovarian cancer has paved the way for a new therapeutic approach aimed at exploiting this unique vulnerability. The efficacy of poly (ADP) ribose polymerase inhibitors (PARPi) in patients with homologous recombination (HR) DNA repair deficient ovarian cancer (OC) resulting from a BRCA1/2 mutation has provided the proof of concept for synthetic lethality. Thus, olaparib is now approved by the EMA as maintenance therapy after response to a platinum regimen for patients with recurrent, platinum-sensitive, high-grade serous, BRCA1/2-mutated ovarian cancer...
October 17, 2017: Bulletin du Cancer
https://www.readbyqxmd.com/read/29054496/cancer-immunotherapy-a-paradigm-shift-in-the-treatment-of-advanced-urologic-cancers
#4
REVIEW
David M Gill, Neeraj Agarwal
The recent resurgence of immunotherapy has transformed the therapeutic field of advanced urologic cancers. In this seminars issue, we evaluate the role of emerging and recently approved immunotherapeutic agents in advanced prostate, urothelial, and renal cell carcinoma. In each of these fields, we discuss recent regulatory approvals as well as promising ongoing clinical trials. Finally, we discuss incidence and management of immune related adverse events specifically associated with PD-1/PD-L1 inhibitors.
October 17, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29053897/scientists-investigate-the-application-of-immunotherapy-to-many-cancer-sites-breast-and-prostate-cancers-prove-more-challenging-but-progress-is-occurring
#5
https://www.readbyqxmd.com/read/29052780/immunotherapy-for-hepatocellular-carcinoma-patients-is-it-ready-for-prime-time
#6
REVIEW
Joseph M Obeid, Paul R Kunk, Victor M Zaydfudim, Timothy N Bullock, Craig L Slingluff, Osama E Rahma
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Current treatment options for patients with intermediate and advanced HCC are limited, and there is an unmet need for novel therapeutic approaches. HCC is an attractive target for immunomodulation therapy, since it arises in an inflammatory milieu due to hepatitis B and C infections and cirrhosis. However, a major barrier to the development and success of immunotherapy in patients with HCC is the liver's inherent immunosuppressive function...
October 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29052609/neuro-ophthalmic-side-effects-of-molecularly-targeted-cancer-drugs
#7
REVIEW
M T Bhatti, A K S Salama
The past two decades has been an amazing time in the advancement of cancer treatment. Molecularly targeted therapy is a concept in which specific cellular molecules (overexpressed, mutationally activated, or selectively expressed proteins) are manipulated in an advantageous manner to decrease the transformation, proliferation, and/or survival of cancer cells. In addition, increased knowledge of the role of the immune system in carcinogenesis has led to the development of immune checkpoint inhibitors to restore and enhance cellular-mediated antitumor immunity...
October 20, 2017: Eye
https://www.readbyqxmd.com/read/29051790/current-immunotherapeutic-strategies-in-hepatocellular-carcinoma-recent-advances-and-future-directions
#8
REVIEW
Hwi Young Kim, Joong-Won Park
Hepatocellular carcinoma (HCC) is a common and serious health problem with high mortality. Treatment for HCC remains largely unsatisfactory owing to its high recurrence rates and frequent accompanying cirrhosis. In addition, the unique immune environment of the liver promotes tolerance, which, in conjunction with immune evasion by the disease, makes HCC a less promising target for conventional immunotherapy. However, recent advances in the immunotherapy have led to novel approaches to overcome these obstacles by manipulating and enhancing tumor-specific immune responses against HCC by using various modalities, such as cancer vaccines and immune checkpoint blockade...
October 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29051489/genomic-landscape-associated-with-potential-response-to-anti-ctla-4-treatment-in-cancers
#9
Chan-Young Ock, Jun-Eul Hwang, Bhumsuk Keam, Sang-Bae Kim, Jae-Jun Shim, Hee-Jin Jang, Sarang Park, Bo Hwa Sohn, Minse Cha, Jaffer A Ajani, Scott Kopetz, Keun-Wook Lee, Tae Min Kim, Dae Seog Heo, Ju-Seog Lee
Immunotherapy has emerged as a promising anti-cancer treatment, however, little is known about the genetic characteristics that dictate response to immunotherapy. We develop a transcriptional predictor of immunotherapy response and assess its prediction in genomic data from ~10,000 human tissues across 30 different cancer types to estimate the potential response to immunotherapy. The integrative analysis reveals two distinct tumor types: the mutator type is positively associated with potential response to immunotherapy, whereas the chromosome-instable type is negatively associated with it...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29051161/prostate-cancer-cells-express-more-androgen-receptor-ar-following-androgen-deprivation-improving-recognition-by-ar-specific-t-cells
#10
Brian M Olson, Melissa Gamat, Joseph Seliski, Thomas Sawicki, Justin Jeffery, Leigh Ellis, Charles G Drake, Jamey Weichert, Douglas G McNeel
Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anti-cancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR...
October 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29050701/cancer-immunotherapy-and-endocrinology-a-new-opportunity-for-multidisciplinary-collaboration
#11
Carles Zafon Llopis
No abstract text is available yet for this article.
November 2017: Endocrinología, diabetes y nutrición
https://www.readbyqxmd.com/read/29050337/comprehensive-immune-transcriptomic-analysis-in-bladder-cancer-reveals-subtype-specific-immune-gene-expression-patterns-of-prognostic-relevance
#12
Runhan Ren, Kathrin Tyryshkin, Charles H Graham, Madhuri Koti, D Robert Siemens
Recent efforts on genome wide profiling of muscle invasive bladder cancer (MIBC) have led to its classification into distinct genomic and transcriptomic molecular subtypes that exhibit variability in prognosis. Evolving evidence from recent immunotherapy trials has demonstrated the significance of pre-existing tumour immune profiles that could guide treatment decisions. To identify immune gene expression patterns associated with the molecular subtypes, we performed a comprehensive in silico immune transcriptomic profiling, utilizing transcriptomic data from 347 MIBC cases from The Cancer Genome Atlas (TCGA)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050282/effective-antitumor-peptide-vaccines-can-induce-severe-autoimmune-pathology
#13
Hussein Sultan, Jimena Trillo-Tinoco, Paulo Rodriguez, Esteban Celis
Immunotherapy has shown a tremendous success in treating cancer. Unfortunately, this success is frequently associated with severe autoimmune pathology. In this study, we used the transgenic RIP-gp mouse model to assess the antitumor therapeutic benefit of peptide vaccination while evaluating the possible associated autoimmune pathology. We report that palmitoylated gp33-41 peptide and poly-IC adjuvant vaccine (BiVax) generated ∼ 5-10 % of antigen specific T cell responses in wild type and supposedly immune tolerant RIP-gp mice...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049237/effect-and-safety-of-cytokine-induced-killer-cik-cell-immunotherapy-in-patients-with-breast-cancer-a-meta-analysis
#14
Jianxin Hu, Junfeng Hu, Xiandong Liu, Chao Hu, Ming Li, Wei Han
BACKGROUND: Breast cancer (BC) is considered a systemic disease with a primarily locoregional component. The accumulation of basic researches and clinical studies related to cytokine-induced killer (CIK) cells has confirmed their safety and feasibility in treating BC. By searching the PubMed, Embase, CNKI, and Wanfang databases, we conducted a meta-analysis to assess the efficacy and safety of DC/CIK plus chemotherapy regimen (Exp) compared with chemotherapy (Con) alone regimen for breast carcinoma...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29048978/antitumor-effect-of-oral-cancer-vaccine-with-bifidobacterium-delivering-wt1-protein-to-gut-immune-system-is-superior-to-wt1-peptide-vaccine
#15
Toshiro Shirakawa, Koichi Kitagawa
Despite the revolutionary progress of immune checkpoint inhibitors (CPIs) for cancer immunotherapy, CPIs are effective only in a subset of patients. Combining CPIs and cancer vaccines to achieve better clinical outcomes is a reasonable approach since CPI enhances cancer vaccine-induced tumor-associated antigen (TAA) specific CTL. Among the various TAAs so far identified, WT1 protein is one of the most promising TAAs as a cancer vaccine target. Until now clinical trials of WT1 vaccine have demonstrated only modest clinical efficacy...
October 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29048671/adoptive-immunotherapy-combined-with-fp-treatment-for-head-and-neck-cancer-an-in%C3%A2-vitro-study
#16
Mayako Nishio-Nagai, Susumu Suzuki, Kazuhiro Yoshikawa, Ryuzo Ueda, Yoshiaki Kazaoka
FP treatment, which combines 5-fluorouracil (5-FU) and cisplatin (CDDP) chemotherapy, is widely used for treatment of advanced head and neck cancer (HNC). It has been suggested that these drugs cause immunomodulation in the cancer microenvironment, for example, downregulation of immunosuppressive cells such as regulatory T-cells (Tregs) and myeloid-derived suppressive cells (MDSCs), activating dendritic cells (DCs), and upregulation of tumor antigens and major histocompatibility complex (MHC) molecules in cancer cells leads to enhancement of cancer immunity, which is important in cancer treatment, as well as providing a direct killing effect...
October 2, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29046677/defining-genome-wide-expression-and-phenotypic-contextual-cues-in-macrophages-generated-by-granulocyte-macrophage-colony-stimulating-factor-macrophage-colony-stimulating-factor-and-heat-killed-mycobacteria
#17
Samer Bazzi, Emale El-Darzi, Tina McDowell, Helmout Modjtahedi, Satvinder Mudan, Marcel Achkar, Charles Akle, Humam Kadara, Georges M Bahr
Heat-killed (HK) Mycobacterium obuense (NCTC13365) is currently being evaluated in the clinic as an immunotherapeutic agent for cancer treatment. Yet, the molecular underpinnings underlying immunomodulatory properties of HK M. obuense are still largely undefined. To fill this void, we sought to perform immunophenotyping, chemokine/cytokine release analysis and genome-wide characterization of monocyte-derived macrophages (MDM) in which monocytes were originally isolated from healthy donors and differentiated by HK M...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29046675/interpreting-t-cell-cross-reactivity-through-structure-implications-for-tcr-based-cancer-immunotherapy
#18
Dinler A Antunes, Maurício M Rigo, Martiela V Freitas, Marcus F A Mendes, Marialva Sinigaglia, Gregory Lizée, Lydia E Kavraki, Liisa K Selin, Markus Cornberg, Gustavo F Vieira
Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient's own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29046454/mechanisms-of-herv-k-hml-2-transcription-during-human-mammary-epithelial-cell-transformation
#19
Meagan Montesion, Neeru Bhardwaj, Zachary H Williams, Charlotte Kuperwasser, John M Coffin
Increasing evidence suggests that repetitive elements may play a role in host gene regulation, particularly through the donation of alternative promoters, enhancers, splice sites, and termination signals. Elevated transcript expression of the endogenous retrovirus group HERV-K (HML-2) is seen in many human cancers, although the identity of the individual proviral loci contributing to this expression as well as their mechanism of activation has been unclear. Using high-throughput next-generation sequencing techniques optimized for the capture of HML-2 expression, we characterized the HML-2 transcriptome and means of activation in an in vitro model of human mammary epithelial cell transformation...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29046389/the-antibody-repertoire-of-colorectal-cancer
#20
Seong Won Cha, Stefano Bonissone, Seungjin Na, Pavel A Pevzner, Vineet Bafna
Immunotherapy is becoming increasingly important in the fight against cancers, utilizing and manipulating the body's immune response to treat tumors. Understanding the immune repertoire - the collection of immunological proteins - of treated and untreated cells is possible at the genomic, but technically difficult at the protein level. Standard protein databases do not include the highly divergent sequences of somatic rearranged immunoglobulin genes, and may lead to missed identifications in a mass spectrometry search...
October 18, 2017: Molecular & Cellular Proteomics: MCP
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