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https://www.readbyqxmd.com/read/29657904/immunotherapy-for-breast-cancer-current-and-future-strategies
#1
Austin D Williams, Kyle K Payne, Avery D Posey, Christine Hill, Jose Conejo-Garcia, Carl H June, Julia Tchou
Purpose of Review: The breast tumor microenvironment is immunosuppressive and is increasingly recognized to play a significant role in tumorigenesis. A deeper understanding of normal and aberrant interactions between malignant and immune cells has allowed researchers to harness the immune system with novel immunotherapy strategies, many of which have shown promise in breast cancer. This review discusses the application of immunotherapy to the treatment of breast cancer. Recent Findings: Both basic science and clinical trial data are rapidly developing in the use of immunotherapy for breast cancer...
December 2017: Current Surgery Reports
https://www.readbyqxmd.com/read/29601471/nanopulse-stimulation-nps-induces-tumor-ablation-and-immunity-in-orthotopic-4t1-mouse-breast-cancer-a-review
#2
REVIEW
Stephen J Beebe, Brittany P Lassiter, Siqi Guo
Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD)...
March 30, 2018: Cancers
https://www.readbyqxmd.com/read/29580807/immunogenicity-and-antitumor-activity-of-the-superlytic-%C3%AE-f7-phage-nanoparticles-displaying-a-her2-neu-derived-peptide-ae37-in-a-tumor-model-of-balb-c-mice
#3
Nastaran Barati, Atefeh Razazan, Jessica Nicastro, Roderick Slavcev, Atefeh Arab, Fatemeh Mosaffa, Amin Reza Nikpoor, Ali Badiee, Mahmoud Reza Jaafari, Javad Behravan
Phage display technique has been increasingly researched for vaccine design and delivery strategies in recent years. In this study, the AE37 (Ii-Key/HER-2/neu 776-790) peptide derived from HER2 (human epidermal growth factor receptor protein) was used as a fused peptide to the lambda phage (λF7) coat protein gpD, and the phage nanoparticles were used to induce antitumor immunogenicity in a TUBO model of breast cancer in mice. Mice were immunized with the AE37 peptide displaying phage, λF7 (gpD::AE37) every 2-week intervals over 6-weeks, then the generated immune responses were evaluated...
March 23, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29576883/rate-of-clinical-complete-response-for-1-year-or-more-in-bone-metastatic-breast-cancer-after-comprehensive-treatments-including-autologous-formalin-fixed-tumor-vaccine
#4
Fumito Kuranishi, Yuki Imaoka, Yuusuke Sumi, Yoji Uemae, Hiroko Yasuda-Kurihara, Takeshi Ishihara, Tsubasa Miyazaki, Tadao Ohno
Introduction: No effective treatment has been developed for bone-metastatic breast cancer. We found 3 cases with clinical complete response (cCR) of the bone metastasis and longer overall survival of the retrospectively examined cohort treated comprehensively including autologous formalin-fixed tumor vaccine (AFTV). Patients and Methods: AFTV was prepared individually for each patient from their own formalin-fixed and paraffin-embedded breast cancer tissues. Results: Three patients maintained cCR status of the bone metastasis for 17 months or more...
2018: International Journal of Breast Cancer
https://www.readbyqxmd.com/read/29574039/phase-ib-trial-of-folate-binding-protein-fbp-derived-peptide-vaccines-e39-and-an-attenuated-version-e39-an-analysis-of-safety-and-immune-response
#5
Timothy J Vreeland, Jennifer K Litton, Na Qiao, Anne V Philips, Gheath Alatrash, Diane F Hale, Doreen O Jackson, Kaitlin M Peace, Julia M Greene, John S Berry, Guy T Clifton, George E Peoples, Elizabeth A Mittendorf
In this randomized phase Ib trial, we tested combining the E39 peptide vaccine with a vaccine created from E39', an attenuated version of E39. Patients with breast or ovarian cancer, who were disease-free after standard of care therapy, were enrolled and randomized to one of three arms. Arm EE received six E39 inoculations; arm EE' received three E39 inoculations followed by three E39'; and arm E'E received three E39' inoculations, followed by three E39. Within each arm, the first five patients received 500 μg of peptide and the remainder received 1000 μg...
March 21, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29572968/implantable-synthetic-immune-niche-for-spatiotemporal-modulation-of-tumor-derived-immunosuppression-and-systemic-antitumor-immunity-postoperative-immunotherapy
#6
Hathaichanok Phuengkham, Chanyoung Song, Soong Ho Um, Yong Taik Lim
The development of biomaterial-based immune niches that can modulate immunosuppressive factors in tumor microenvironment (TME) will be a key technology for improving current cancer immunotherapy. Here, implantable, engineered 3D porous scaffolds are designed to generate synergistic action between myeloid-derived suppressor cell (MDSC)-depleting agents, which can accommodate the establishment of a permissive immunogenic microenvironment to counteract tumor-induced immunosuppression, and cancer vaccines consisting of whole tumor lysates and nanogel-based adjuvants, which can generate tumor antigen-specific T cell responses...
March 23, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29545464/folate-receptor-alpha-peptide-vaccine-generates-immunity-in-breast-and-ovarian-cancer-patients
#7
Kimberly R Kalli, Matthew S Block, Pashtoon M Kasi, Courtney L Erskine, Timothy J Hobday, Allan Dietz, Douglas Padley, Michael P Gustafson, Barath Shreeder, Danell Puglisi-Knutson, Daniel W Visscher, Toni Kay Mangskau, Glynn Wilson, Keith L Knutson
PURPOSE: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients...
March 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29515795/a-phase-1-2-study-of-adenovirus-p53-transduced-dendritic-cell-vaccine-in-combination-with-indoximod-in-metastatic-solid-tumors-and-invasive-breast-cancer
#8
Hatem Soliman, Fatema Khambati, Hyo S Han, Roohi Ismail-Khan, Marilyn M Bui, Daniel M Sullivan, Scott Antonia
Background: Indoleamine 2, 3-dioxygenase is an enzyme that causes immunosuppression in tumors. Indoximod inhibits the indoleamine 2, 3-dioxygenase pathway and enhances immunologic responses to dendritic cell (DC) vaccines preclinically. Adenovirus p53 (Ad.p53) is used to generate DC vaccines against p53. A phase-1/2 trial of indoximod with Ad.p53-DC vaccine was conducted. Materials and Methods: The phase-1 study combined 7 indoximod dose levels with < 6 Ad.p53-DC vaccinations every 2 weeks...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29468855/major-clinical-research-advances-in-gynecologic-cancer-in-2017
#9
REVIEW
Dong Hoon Suh, Miseon Kim, Kyung Hun Lee, Keun Yong Eom, Maj Kamille Kjeldsen, Mansoor Raza Mirza, Jae Weon Kim
In 2017, 10 topics were selected as major clinical research advances in gynecologic oncology. For cervical cancer, efficacy and safety analysis results of a 9-valent human papillomavirus (HPV) vaccine and long-term impact of reduced dose of quadrivalent vaccine were updated. Brief introduction of KEYNOTE trials of pembrolizumab, a monoclonal antibody that blocks the interaction between programmed death (PD)-1 and its ligands, PD-L1 and PD-L2, followed. Tailored surveillance programs for gynecologic cancer related with Lynch syndrome and update on sentinel lymph node mapping were reviewed for uterine corpus cancer...
March 2018: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/29465777/expression-of-mage-a-and-ny-eso-1-cancer-testis-antigens-is-enriched-in-triple-negative-invasive-breast-cancers
#10
Ashwini Raghavendra, Priyakshi Kalita-de Croft, Ana Cristina Vargas, Chanel E Smart, Peter T Simpson, Jodi M Saunus, Sunil R Lakhani
AIMS: A better understanding of the expression of cancer testis antigens (CTA) in breast cancer might identify new immunotherapy options, especially for triple-negative (TN) tumours, which lack expression of conventional therapeutic targets ER, PR and HER2 (receptors for Oestrogen, Progesterone and Human epidermal growth factor). The aim of this study was to quantify the expression of MAGE-A and NY-ESO-1 CTAs in breast cancer, and relate this to known clinicopathologic parameters. METHODS AND RESULTS: We surveyed MAGE-A and NY-ESO-1 protein expression in an unselected cohort of 367 breast tumours (out of which 65 tumours were TN), with accompanying clinical follow-up data, using immunohistochemistry (IHC) analysis of tissue microarrays...
February 21, 2018: Histopathology
https://www.readbyqxmd.com/read/29462389/neoplasia-and-precursor-lesions-of-the-female-genital-tract-in-ibd-epidemiology-role-of-immunosuppressants-and-clinical-implications
#11
Hanna M J L Hazenberg, Nanne K H de Boer, Chris J J Mulder, Stijn H Mom, Ad A van Bodegraven, Greetje J Tack Md PhD
In this review the risk of breast, ovarian, and endometrial cancer and cervical and vulvovaginal (pre)malignant abnormalities in patients with inflammatory bowel disease (IBD) with or without immune suppressive treatment will be discussed. So far, this has not been studied thoroughly and large studies taking into account diverse potential confounding factors are lacking. IBD per se has not been associated with development of cervical cancer, yet patients with Crohn's disease who smoke, have a younger age at diagnosis or who use(d) thiopurines might be more at risk...
February 15, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29456158/autologous-ipsc-based-vaccines-elicit-anti-tumor-responses-in-vivo
#12
Nigel G Kooreman, Youngkyun Kim, Patricia E de Almeida, Vittavat Termglinchan, Sebastian Diecke, Ning-Yi Shao, Tzu-Tang Wei, Hyoju Yi, Devaveena Dey, Raman Nelakanti, Thomas P Brouwer, David T Paik, Idit Sagiv-Barfi, Arnold Han, Paul H A Quax, Jaap F Hamming, Ronald Levy, Mark M Davis, Joseph C Wu
Cancer cells and embryonic tissues share a number of cellular and molecular properties, suggesting that induced pluripotent stem cells (iPSCs) may be harnessed to elicit anti-tumor responses in cancer vaccines. RNA sequencing revealed that human and murine iPSCs express tumor-associated antigens, and we show here a proof of principle for using irradiated iPSCs in autologous anti-tumor vaccines. In a prophylactic setting, iPSC vaccines prevent tumor growth in syngeneic murine breast cancer, mesothelioma, and melanoma models...
April 5, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29441705/injectable-tough-alginate-cryogels-as-cancer-vaccines
#13
Ting-Yu Shih, Serena O Blacklow, Aileen W Li, Benjamin R Freedman, Sidi Bencherif, Sandeep T Koshy, Max C Darnell, David J Mooney
A covalently crosslinked methacrylated (MA)-alginate cryogel vaccine has been previously shown to generate a potent response against murine melanoma, but is not mechanically robust and requires a large 16G needle for delivery. Here, covalent and ionic crosslinking of cryogels are combined with the hypothesis that this will result in a tough MA-alginate cryogel with improved injectability. All tough cryogels can be injected through a smaller, 18G needle without sustaining any damage, while covalently crosslinked-only cryogels break after injection...
February 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29434859/silencing-of-suppressor-of-cytokine-signaling-1-enhances-the-immunological-effect-of-mucin-1-calreticulin-primed-4t1-cell-treated-dendritic-cells-in-breast-cancer-treatment
#14
Song Qin, Zhipeng Gao, Yu Liu, Changbai Liu, Jun Wang, Li Li Zou
In cancer immunotherapy, dendritic cell (DC)-based vaccines represent a promising, yet challenging, treatment method. In addition to overcoming the low expression levels of antigenic epitopes on cancer cells, it is also necessary to overcome the inhibitory effect of suppressor of cytokine signaling 1 (SOCS1) on DC self-antigen presentation. Our group previously demonstrated that calreticulin (CRT) translocated type I transmembrane glycoprotein mucin 1 (MUC1), a breast cancer antigen, to the surface of 4T1 cells, and that treatment with MUC1-CRT-primed 4T1 cell-treated DCs induced apoptosis in a breast cancer cell line...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29424297/use-of-immunotherapy-to-treat-metastatic-breast-cancer
#15
Andrea Nicolini, Vivian Barak, Piermario Biava, Paola Ferrari, Giuseppe Rossi, Angelo Carpi
This article reviews the principal attempts of immune-modulation or immune therapy in metastatic breast cancer. It considers their rationale and reports on results from the relevant key clinical trials. Immune-modulatory or immune-stimulating cytokines used alone or combined with conventional therapies is among the principal approaches of immune manipulation in breast cancer. As this issue was recently reviewed by us, the aim of the current article is to discuss our updated and unpublished data on this topic...
February 9, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29415817/heterologous-human-rat-her2-specific-exosome-targeted-t-cell-vaccine-stimulates-potent-humoral-and-ctl-responses-leading-to-enhanced-circumvention-of-her2-tolerance-in-double-transgenic-hla-a2-her2-mice
#16
Yufeng Xie, Jie Wu, Aizhang Xu, Shahid Ahmeqd, Amer Sami, Rajni Chibbar, Andrew Freywald, Changyu Zheng, Jim Xiang
DNA vaccines composed of heterologous human HER2 and rat neu sequences induce stronger antibody response and protective antitumor immunity than either HER2 or neu DNA vaccines in transgenic mice. We previously developed HER2-specific exosome-targeted T-cell vaccine HER2-TEXO capable of stimulating HER2-specific CD8+ T-cell responses, but only leading to partial protective immunity in double-transgenic HLA-A2/HER2 mice with self-immune tolerance to HER2. Here, we constructed an adenoviral vector AdVHuRt expressing HuRt fusion protein composed of NH2-HER21-407 (Hu) and COOH-neu408-690 (Rt) fragments, and developed a heterologous human/rat HER2-specific exosome-targeted T-cell vaccine HuRt-TEXO using polyclonal CD4+ T-cells uptaking exosomes released by AdVHuRt-transfected dendritic cells...
February 5, 2018: Vaccine
https://www.readbyqxmd.com/read/29404275/oncogenic-viruses-and-breast-cancer-mouse-mammary-tumor-virus-mmtv-bovine-leukemia-virus-blv-human-papilloma-virus-hpv-and-epstein-barr-virus-ebv
#17
REVIEW
James S Lawson, Brian Salmons, Wendy K Glenn
Background: Although the risk factors for breast cancer are well established, namely female gender, early menarche and late menopause plus the protective influence of early pregnancy, the underlying causes of breast cancer remain unknown. The development of substantial recent evidence indicates that a handful of viruses may have a role in breast cancer. These viruses are mouse mammary tumor virus (MMTV), bovine leukemia virus (BLV), human papilloma viruses (HPVs), and Epstein-Barr virus (EBV-also known as human herpes virus type 4)...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29399414/virus-like-particle-display-of-her2-induces-potent-anti-cancer-responses
#18
Arianna Palladini, Susan Thrane, Christoph M Janitzek, Jessica Pihl, Stine B Clemmensen, Willem Adriaan de Jongh, Thomas M Clausen, Giordano Nicoletti, Lorena Landuzzi, Manuel L Penichet, Tania Balboni, Marianna L Ianzano, Veronica Giusti, Thor G Theander, Morten A Nielsen, Ali Salanti, Pier-Luigi Lollini, Patrizia Nanni, Adam F Sander
Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20-30% of invasive breast cancers. Monoclonal antibody therapy is effective in treating HER2-driven mammary carcinomas, but its utility is limited by high costs, side effects and development of resistance. Active vaccination may represent a safer, more effective and cheaper alternative, although the induction of strong and durable autoantibody responses is hampered by immune-tolerogenic mechanisms. Using a novel virus-like particle (VLP) based vaccine platform we show that directional, high-density display of human HER2 on the surface of VLPs, allows induction of therapeutically potent anti-HER2 autoantibody responses...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399164/prognostic-significance-of-expression-of-epithelial-mesenchymal-transition-driver-brachyury-in-breast-cancer-and-its-association-with-subtype-and-characteristics
#19
Kwan Ho Lee, Eun Young Kim, Ji Sup Yun, Yong Lai Park, Sung-Im Do, Seoung Wan Chae, Chan Heun Park
Brachyury is a T-box transcription factor characterized as a driver of the epithelial-to-mesenchymal process, which is associated with poor prognosis of patients with breast cancer. The present study investigated expression of brachyury in breast cancer including primary tumor, metastatic and recurred tumor tissues, and the clinical significance and value of brachyury as a prognostic biomarker. This retrospective study included a series of 102 consecutive patients surgically resected between January 2005 and December 2011...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29375131/a-modified-hla-a-0201-restricted-ctl-epitope-from-human-oncoprotein-hpebp4-induces-more-efficient-antitumor-responses
#20
Weihong Sun, Junyi Shi, Jian Wu, Junchu Zhang, Huabiao Chen, Yuanyuan Li, Shuxun Liu, Yanfeng Wu, Zhigang Tian, Xuetao Cao, Nan Li
We previously identified human phosphatidylethanolamine-binding protein 4 (hPEBP4) as an antiapoptotic protein with increased expression levels in breast, ovarian and prostate cancer cells, but low expression levels in normal tissues, which makes hPEBP4 an attractive target for immunotherapy. Here, we developed hPEBP4-derived immunogenic peptides for inducing antigen-specific cytotoxic T lymphocytes (CTLs) targeting breast cancer. A panel of hPEBP4-derived peptides predicted by peptide-MHC-binding algorithms was evaluated to characterize their HLA-A2...
January 29, 2018: Cellular & Molecular Immunology
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