bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B107: In vivo mouse breast cancers-xenograft imaging with radiolabeled recombinant Flagellin
Authors: Hou Guihua 
Published: May 2016

Abstract
Recently it was noted that Toll-like receptor 5 (TLR5), the only protein recognition receptor of TLRs, high expressed in breast cancers and closely related to tumor development. In this study, we aimed to evaluate whether TLR5 could serve as a molecular target for breast cancer monitoring.
BALB/c mice were implanted with breast cancer line MCF-7 to establish a tumor-bearing mice model. Dynamic whole-body phosphor-autoradiography in vivo and ex vivo biodistribution studies were performed after 131I-recombinant Flagellin (rFliC, a specific ligand of TLR5) injection through the tail vein.
131I- rFliC was successfully prepared with Iodogen method. The uptake of MCF-7 to 131I-rFliC was quickly, and reached the highest point at 6h. Dynamic phosphor-autoradiography imaging showed clear tumor localization of tracer from 1 h onward. At 6 h after injection, tumor uptake was the highest. Pre-treatment with anti-TLR5 mAb obviously blocked tumor uptake of tracer. Biodistribution study reflected the same tendency, and obviously 131I- rFliC uptake of tumor was obtained at 3h after tracer injection, and reached a maximum of T/NT ratio(tumor to muscle,7.09 ± 1.86 %ID/g (percent injected dose per gram) at 24 h compared with naïve mice. Immunohistochemistry staining showed higher expression of TLR5 in tumor tissue, supported the results of phosphor-autoradiographagy and ex vivo biodistrbution studies.
These data suggested that radiolabeled rFliC could quickly localise in tumor tissue, which may be as a new tracer for non-invasive in vivo imaging of TLR5 in breast cancer.
Citation Format: Guihua Hou. In vivo mouse breast cancers-xenograft imaging with radiolabeled recombinant Flagellin. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B107.
Abstract B121: Low dose, metronomic cyclophosphamide therapy sensitizes tumors to CpG-1826 immunotherapy in a preclinical glioma model
Authors: Jordan Marie , Waxman David J. 
Published: May 2016

Abstract
Metronomic chemotherapy, in which cytotoxic drugs are delivered at low doses at regular, intermittent intervals, has shown promising clinical results in several cancers and offers the benefit of reduced patient toxicity compared to conventional maximum tolerated dose chemotherapy. We previously showed that cyclophosphamide (CPA) treatment on a 6-day repeating metronomic schedule regresses implanted gliomas by an immune-mediated mechanism. Here, we examine whether this immune-stimulatory metronomic chemotherapy can be enhanced by combination with TLR9-stimulating CpG-1826 immunotherapy in GL261 gliomas implanted in immunocompetent BL6 mice. CpG-1826 treatment activated an anti-tumor immune response in ~50% of mice, associated with a strong increase in tumor-associated macrophages. CpG-1826 was ineffective against GL261 tumors implanted in T cell- and B cell-deficient scid mice, suggesting that adaptive immunity is essential. Combination of CpG-1826 with metronomic CPA sensitized GL261 gliomas in both CpG-1826-responsive and CpG-1826-non-responsive mice, increasing infiltration of tumor-associated macrophages, dendritic cells, and T cells and increasing anti-tumor activity. Further, the combination treatment elicited long-term regression and immune memory in a subset of glioma-bearing mice. To identify potential mechanisms for this enhanced response to the combination therapy, we assayed a number of immune-related genes in the treated tumors, including feedback inhibitory immunosuppressive T cell factors that are induced by metronomic CPA treatment. Combination of CpG-1826 with metronomic CPA failed to induce several of these factors, suggesting that TLR9-based immunotherapy can enhance the anti-tumor activity of metronomic CPA by interdicting feedback immune inhibition mechanisms. Grant support: CA49248 (to DJW).
Citation Format: Marie Jordan, David J. Waxman. Low dose, metronomic cyclophosphamide therapy sensitizes tumors to CpG-1826 immunotherapy in a preclinical glioma model. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B121.
Abstract B122: A preclinical mouse model to assess antitumor efficacy and development of immune related adverse events (irAEs) following combination immunotherapies
Authors: Liu Jing , Blake Stephten J. , Fairfax Kirsten A. , Yong Michelle C.R. , Allen Stacey , Smyth Mark J. , Teng Michele W.L. 
Published: May 2016

Abstract
Given that new immunotherapies in combination are displaying both efficacy and immune related adverse events (irAEs) in humans, there is a need to promptly develop a pre-clinical mouse model that can evaluate the therapeutic index (efficacy versus safety) of current and novel immunotherapies. We demonstrated that transient or prolonged T regulatory cell (Treg) depletion in tumor bearing Foxp3-DTR mice using diphtheria toxin (DT) mirrored the spectrum of anti-tumor responses and severity of irAEs that can occur in ipilimumab/nivolumab treated patients. We showed that transient Treg depletion with DT in combination with anti-PD-1 or anti-TIM-3 monoclonal antibodies (mAbs) had a high therapeutic index compared to DT plus anti-CD137. While all three mAbs suppressed tumor growth, tumor rejection was more frequently observed in the DT plus anti-PD-1 or DT plus anti-TIM-3 combinations, depending on the tumor type, and these mice developed only mild irAEs. In contrast, mice treated with DT plus anti-CD137 developed severe irAEs characterized by infiltration of activated T cells into peripheral organs, liver toxicities and elevated levels of inflammatory cytokines, similar to grade 3/4 clinical symptoms. These irAEs appeared due to an infiltration of activated proliferating effector T cells in the tissues producing IFNγ and TNF, however, TNF blockade decreased the severity of irAEs in these mice without impacting on tumor growth. This model may now be used to pre-clinically assess the therapeutic indices of novel immunotherapy combinations to understand their mechanism of action and safety.
Citation Format: Jing Liu, Stephten J. Blake, Kirsten A. Fairfax, Michelle C.R. Yong, Stacey Allen, Mark J. Smyth, Michele W.L. Teng. A preclinical mouse model to assess antitumor efficacy and development of immune related adverse events (irAEs) following combination immunotherapies. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B122.
Abstract B130: Evaluation of novel metronomic chemotherapy and cancer vaccine combinatorial strategy
Authors: Tagliamonte Maria , Petrizzo Annacarmen , Tornesello Maria Lina , Luciano Antonio , Rea Domenica , Barbieri Antonio , Arra Claudio , Napolitano Maria , Ciliberto Gennaro , Aurisicchio Luigi , Coscia Claudio , Baechle Tobias , Buonaguro Franco M. , Buonaguro Luigi 
Published: May 2016

Abstract
The efficacy of cancer immunotherapy approaches can be significantly hampered by the tumor immune suppressive microenvironment. In the present study, a novel combinatorial strategy (i.e. metronomic chemotherapy plus vaccine) is evaluated in a mouse model in an aggressive therapeutic setting based on sub-cutaneous ectopic implantation of B16 melanoma cells. The chemotherapy is a multi-drug cocktail including taxanes and alkylating agents, administered in a daily metronomic fashion. The vaccine is a multi-peptide cocktail of universal tumor antigen hTERT epitopes adjuvanted in Montanide.
Immunizations have been performed comparing a standard sub-cutaneous delivery with a laser-assisted epidermal immunogen delivery by P.L.E.A.S.E.™ Professional (Pantec Biosolutions). The latter, indeed, creates evenly distributed micropores through to the epidermis and provides a great opportunity to efficiently deliver vaccine antigens to Langerhans cells (LC) in the epidermis.
An interim analysis shows that the immunogenicity as well as the therapeutic effect on tumor growth of the vaccine is significantly increased by the combination with metronomic chemotherapy, and the laser-assisted epidermal immunogen delivery appears to be a very effective strategy as vaccine delivery. Complete description of both immunogenicity and therapeutic effects on tumor growth will be described.
Citation Format: Maria Tagliamonte, Annacarmen Petrizzo, Maria Lina Tornesello, Antonio Luciano, Domenica Rea, Antonio Barbieri, Claudio Arra, Maria Napolitano, Gennaro Ciliberto, Luigi Aurisicchio, Claudio Coscia, Tobias Baechle, Franco M. Buonaguro, Luigi Buonaguro. Evaluation of novel metronomic chemotherapy and cancer vaccine combinatorial strategy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B130.
Abstract B150: Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network
Authors: Lu Haihui , Tam Wai Leong , Donnenberg Vera , Ye Xin , Bhargava Rohit , Weinberg Robert 
Published: May 2016

Abstract
The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. In addition, EMT upregulates the expression of cell surface receptors that enable CSCs to interact with their surrounding microenvironment in order to sustain their stem cell state. We discovered that EphA4 and CD90, two cell surface proteins upregulated in the carcinoma cells by the EMT, mediate juxtacrine signalling between the CSCs and tumor-associated monocytes and macrophages (TAMs). When engaged with its counter-receptor on TAMs, EphA4 on the CSCs activates Src and PLCγ1, the latter resulting in the translocation of NF-κB into the nucleus, which cooperates with Twist to drive the rapid induction of a variety of cytokines in the CSCs. Among the secreted cytokines IL-8 and IL-6 maintain the CSC-state by reinforcing the expression of the EMT-inducing transcription factors, whereas other cytokines GM-CSF, M-CSF and IL-10 recruit monocytes and induce their differentiation into M2-like macrophages. Together these cytokines perpetuate the CSC-promoting interactions between CSCs and TAMs. Indeed, admixed TAMs promote the tumor-initiating ability of CSCs whereas ablation of endogenous macrophages substantially diminished tumor initiation. Importantly, the juxtaposition of TAMs with the mesenchymal-like CD90high CSCs can be observed at the invading edge in primary human breast tumor sections and xenograft tumors. On the contrary, we rarely find TAMS infiltrating beyond the edge of tumors into the regions where the CD90neg non-stem carcinoma cells reside. These findings underscore the importance of TAMs as critical components of the CSC niche and highlight their potential as therapeutics targets.
Citation Format: Haihui Lu, Wai Leong Tam, Vera Donnenberg, Xin Ye, Rohit Bhargava, Robert Weinberg. Juxtacrine signaling between the tumor-associated macrophages and the breast cancer stem cells contribute to the cancer stem cell niche by inducing a cytokine signaling network. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B150.
Abstract IA03: Antitumor activity of immunomodulatory antibodies
Authors: Korman Alan J. 
Published: May 2016

Abstract
Immunomodulatory antibodies activate antitumor responses through multiple mechanisms. These include activation of T cells through the inhibition of negative T cell regulators (known as checkpoint blockade), as well as through the engagement of T cell costimulatory receptors with agonistic antibodies. Antibodies which block CTLA-4 function through inhibition of ligand binding were observed to derive much of their anti-tumor activity through the engagement of activating Fc receptors (Selby et al. Cancer Imm Res 2013; Simpson et al. J Exp Med 2013). This activity was due to the depletion of CTLA-4-positive regulatory T cells uniquely at the tumor site. Related observations for agonistic antibodies to GITR and OX40 (Bulliard et al. J Exp Med 2013, Bulliard et al. Immunol Cell Biol 2014) have led to the reevaluation of the mechanism of action of many immunomodulatory antibodies. We have extended the study of the role of immunoglobulin isotype on the mechanism of action of antibodies to a variety of negative regulators, including PD-1 and PD-L1, and multiple costimulatory molecules, including CD137. In addition, the role of human IgG2 hinge variants on the properties of immunomodulatory antibodies has also been studied. These results have significant impact on the design of therapeutic antibodies. The development of antibodies in which specific T cell functions are targeted will lead to superior choices in considerations for combination cancer immunotherapy.
Citation Format: Alan J. Korman. Antitumor activity of immunomodulatory antibodies. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA03.
Abstract IA06: Targeting the mutanome for individualized cancer immunotherapy
Authors: Sahin Ugur 
Published: May 2016

Abstract
Mutations are regarded as ideal targets for cancer immunotherapy. As neo-epitopes with strict lack of expression in any healthy tissue, they are expected to be safe. The systematic use of mutations for vaccine approaches, however, is hampered by the uniqueness of the repertoire of mutations (the mutanome) in every patient's tumor. We have recently proposed a personalized immunotherapy approach targeting the spectrum of individual mutations. Preclinically we could show in three independent murine tumor models that a considerable fraction of non-synonymous cancer mutations is immunogenic and that unexpectedly the immunogenic mutanome is pre-dominantly recognized by CD4+ T cells (the CD4+ immunome). Vaccination with such CD4+ immunogenic mutations confers strong antitumor activity. Encouraged by these findings we set up a process comprising mutation detection by exome sequencing, selection of vaccine targets by solely bioinformatical prioritization of mutated epitopes predicted to be abundantly expressed and good MHC class II binders and rapid production of synthetic mRNA vaccines encoding multiple of these mutated epitopes. We show that vaccination with such poly-neo-epitopic mRNA vaccines induces potent tumor control and complete rejection of established aggressively growing tumors in mice.
End of 2013 this approach has been translated from bench to bedside when a first in human clinical study started demonstrating the clinical feasibility of the approach (NCT02035956). This tailored immunotherapy approach may be regarded as a universally applicable blueprint for comprehensive exploitation of the huge neo-epitope target repertoire of cancers enabling the treatment of patients by targeting every patient's tumor with individual just in time produced vaccines.
Citation Format: Ugur Sahin. Targeting the mutanome for individualized cancer immunotherapy. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA06.
Abstract IA24: Immune checkpoint therapy: Immune monitoring on presurgical and tissue-based clinical trials
Authors: Sharma Padmanee 
Published: May 2016

Abstract
Immune checkpoint therapies, including anti-CTLA-4, anti-PD-1 and anti-PD-L1, have led to significant clinical responses in cancer patients. To investigate immunologic changes and mechanistic pathways that are elicited by these therapies, we conducted pre-surgical clinical trials, which permit access to sufficient tumor tissues for laboratory studies. The first pre-surgical trial was conducted with anti-CTLA-4 (ipilimumab) in a cohort of patients with localized bladder cancer. This trial provided access to sufficient tumor-infiltrating lymphocytes to conduct phenotypic and functional studies on these cells, which indicated the ICOS/ICOSL pathway as relevant for anti-tumor immune responses in the setting of anti-CTLA-4 therapy. In addition, since standard agents that enable tumor cell death may allow for priming of a T cell immune response that can be augmented by combination with CTLA-4 blockade, we conducted a pre-surgical clinical trial with androgen deprivation (hormonal) therapy ADT+ anti-CTLA-4 (ipilimumab), in the setting of patients with regional, high-risk prostate cancer. These pre-surgical clinical trials, and other tissue-based clinical trials, led to the identification of biomarkers and additional targets. These data, which are being used to design future immunotherapy trials, will be discussed in greater details.
Citation Format: Padmanee Sharma. Immune checkpoint therapy: Immune monitoring on presurgical and tissue-based clinical trials. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA24.
Abstract IA38: Engineered T cell-receptor based therapy of pancreatic ductal adenocarcinoma
Authors: Stromnes Ingunn M. , Schmitt Thomas M. , Brockenbrough Scott J. , Nguyen Hieu , Cuevas Carlos , Hulbert Ayaka , Hotes Jennifer , Dotson Ashley , Hingorani Sunil R. , Greenberg Philip D. 
Published: May 2016

Abstract
Pancreatic ductal adenocarcinoma (PDA) presents a formidable challenge for effective therapies given the robust desmoplasia, immunosuppressive elements and relatively few coding mutations characteristic of this disease. We demonstrate the safety and therapeutic activity of T cells engineered to express an affinity-enhanced T cell receptor (TCR) targeting the naturally overexpressed self/tumor antigen Mesothelin in an autochthonous, genetically engineered mouse model of PDA (KPC). Notably, despite the hostile tumor microenvironment surrounding PDA, the engineered T cells readily infiltrate the desmoplastic tumor, induce tumor cell lysis and remodel the tumor extracellular matrix without causing detectable toxicity in normal tissues. The transferred T cells persist in PDA, but antitumor activity is transient, as the tumor-infiltrating donor T cells upregulate a panel of inhibitory receptors and become progressively dysfunctional specifically in PDA that is due to both TCR-dependent and independent mechanisms of inhibition. This obstacle to sustained therapeutic activity can be overcome by serial T cell infusions, which mediate objective responses and a near doubling of KPC survival without overt toxicities. Similarly engineered human T cells recognize and lyse PDA cells in vitro, further supporting the clinical advancement of this TCR-based strategy for the treatment of human PDA.
Citation Format: Ingunn M. Stromnes, Thomas M. Schmitt, Scott J. Brockenbrough, Hieu Nguyen, Carlos Cuevas, Ayaka Hulbert, Jennifer Hotes, Ashley Dotson, Sunil R. Hingorani, Philip D. Greenberg. Engineered T cell-receptor based therapy of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr IA38.
Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank
Authors: Escuder-Vieco Diana , Garcia-Algar Óscar , Joya Xavier , Marchei Emilia , Pichini Simona , Pacifici Roberta , Pallás-Alonso Carmen Rosa 
Published: May 2016

Background: The use of illegal drugs and tobacco is an exclusion criteria for accepting a nursing mother as a milk donor. The detection window for human milk testing is typically a few hours. Hair testing has been considered the gold standard to assess chronic exposure to these toxic substances. Objective: The aim of this study was to determine the levels of illegal drugs, nicotine, and caffeine in breast milk and hair samples from donors to assess whether these substances were being used during the donation period and the months leading up to it. Methods: Thirty-six samples of hair and breast milk were obtained from 36 donors. The tests performed identified nicotine, caffeine, morphine, cocaine, cannabis, amphetamines, codeine, methadone, and other substances derived therefrom. Results: No illegal drugs were found in any of the samples analyzed. Nicotine and cotinine were found in 33.3% (12/36) of all hair samples. Among these 12 samples, 10 had cotinine concentrations consistent with cutoff values for unexposed nonsmokers, 1 had concentrations consistent with cutoff values for passive smokers, and 1 had concentrations consistent with cutoff values for active smokers. Caffeine was found in 77.7% of the hair samples and in 50% of the donor milk samples. The correlation for caffeine between donor milk and hair samples was r = 0.288, P = .0881. Conclusion: Donors do not use illegal drugs during either the donation period or the months leading up to it. They are occasionally exposed to tobacco smoke and almost all of them consume caffeine.
“Impact of Institutional Changes Felt by Faculty Members”: A Study with Reference to Management Institutes in Pune City
Authors: Apte Anand 
Published: May 2016

Management Institutes are changing over the last decade because of competition, changes in technology, teaching pedagogy, and placement expectations from students and value for money for their parents. The next decade will bring even greater change impacting on all facets of the management institutes including major changes in infrastructure facilities, role of director, faculty members, and students of the management institutes. Changes may take place because of placement of students, faculty member’s attitude toward students and institute etc. It is up to the management of the institute to see how effectively and smoothly these changes could be done to face competition. In this research paper an attempt has been made to know the need and types of changes required, effect of changes on faculty members and management institutes, and understanding and solving the difficulties in implementing changes in the management institutes. For this research paper 60 faculty members were covered from management institutes in Pune. It is a descriptive research and convenience sampling was used. Primary data were collected from questionnaires. Secondary data were collected from journals, magazines, and web sites. Data analysis and hypothesis testing were done. The study revealed that faculty members like the changes made by the institute, changes are due to less admissions and adopting new technology/methodology. Difficulties/problems for implementing the changes are: Barriers in communication, interpersonal relationship, no role clarity, not understanding the necessity for change, and not accepting responsibility for change.