bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B140: Positron emission tomography-guided photodynamic therapy with biodegradable silica nanoparticles for personalized cancer immunotherapy
Authors: Xu Cheng , Moon James 
Published: February 2019

Abstract
Recent clinical trials with neoantigen-based vaccines have shown the feasibility and potential of personalized cancer immunotherapy. Photodynamic therapy (PDT), which utilizes photosensitizer and laser irradiation to produce reactive oxygen species, has been widely explored for local cancer treatment. In addition, positron emission tomography (PET) is a highly sensitive and noninvasive imaging method that can visualize solid tumors while allowing for quantitative analysis of drug biodistribution. In this work, we aimed to combine vaccination and PET imaging-guided PDT as an effective combination platform for personalized cancer immunotherapy. We have synthesized biodegradable silica nanoparticles (bMSN) loaded with neoantigen, CpG oligodeoxynucleotide (a potent Toll-like recetor-9 agonist) and chlorin e6 (a widely used photosensitizer). Using PET imaging, we have shown that bMSN effectively accumulates in MC-38 colon carcinoma tumors after intravenous administration in vivo. Subsequent PDT with 660 nm laser irradiation eliminated tumors, resulting in the release of tumor antigens and danger signals that promoted recruitment of dendritic cells to PDT-treated sites. The bMSN nanoplatform sustain-released neoantigen and CpG oligodeoxynucleotide, while activating DCs and enhancing neoantigen-specific cytotoxic CD8+ T-cell responses and their infiltration into tumors. In mice bearing two contralateral MC-38 tumors, the combination of vaccination and PDT completely eradicated locally treated, large MC-38 tumors while significantly delaying the growth of distant, untreated tumors. Our findings suggest that bMSN is a promising immunotherapeutic platform for combining imaging, vaccination, and PDT for treatment of advanced cancer.
Citation Format: Cheng Xu, James Moon. Positron emission tomography-guided photodynamic therapy with biodegradable silica nanoparticles for personalized cancer immunotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B140.
Abstract B143: Lace molecular vaccine with adjuvant booster to enhance immunogenicity
Authors: Yu Chunson , Liu Haipeng 
Published: February 2019

Abstract
Manipulation of vaccine adjuvants, including bioconjugation and particle formulation, is a prevailing approach to achieve efficient delivery and improve therapeutic efficacy. However, these approaches may compromise bioactivity or may not be desirable when these compounds are chemically or physically unmanipulable. Here, we report an “adjuvant booster” strategy to markedly promote immunogenicity by simply lacing molecular vaccines with an adjuvant booster. We created an adjuvant booster, lipid modified 20-mer thymidine oligodeoxynucleotide (lipo T20), which could significantly increase the potency of Toll-like receptor 7 (TLR7) ligands in both murine and human TLR7 HEK 293 cells and substantially target draining lymph nodes where unmodified adjuvant rarely accumulated. Subcutaneous administration of “imiquimod/protein antigen” vaccine laced with lipo T20 in mice resulted in a five-fold increase in T-cell priming and enhanced antibody response in comparison to booster-free vaccine. “Adjuvant booster” strategy provides an alternative and simple methodology to further enhance immunogenicity of molecular vaccines.
Citation Format: Chunson Yu, Haipeng Liu. Lace molecular vaccine with adjuvant booster to enhance immunogenicity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B143.
Abstract B144: Morphologic consequences for noncapsular lymphoid tissue in the case of malignancy of GERD (Barrett's esophagus)
Authors: Azhken Bakhtiyar Talgatuly 
Published: February 2019

Abstract
In this case, the process of development of the Barrett's esophagus and the development of adenocarcinoma as a complication of this disease with involvement of lymphoid tissue with the formation of follicles of different types was studied. Barrett's esophagus (BE) is a precursor of adenocarcinoma of the esophagus, a disease with a growing burden in the Western world. The incidence of BE increased dramatically during the late 20th century and increased morbidity of this disease. Prevalence is between 0.5 and 2.0%. There are risk factors for BE, including obesity and tobacco smoking, but gastroesophageal reflux disease (GERD) is the strongest risk factor. Adenocarcinoma of the esophagus (ACE) is the most common form of esophageal cancer. However, the data from United Kingdom and the Netherlands show that the incidence of BE increased even after monitoring the increase in endoscopy indices. These estimates indicate an increase in the incidence of BE in approximately 65% between 1997 and 2002 and 159% between 1993 and 2005. It is disturbing that the greatest proportionate increase in the diagnosis of BE was in people younger than 60 years, which is consistent with other works from Europe. In analyzing the literature relating to the intrinsic glands of the esophagus and Barrett esophagus, concerned the esophagus's own glands and the presence of a large number of endocrine cells in them. N.I. Kolycheva, R.R. Bektayeva studied at ultramicroscopic level. When studying the work on the lymphoid formations of the esophagus, we can cite, concerning the lymphoid component of the esophagus. At present, the source of lymphocyte infiltration into its proper mucous plate, types of lymphoid formations, has not been studied. To study the lymphoid noncapsular formations of the mucous membrane of Barrett's esophagus, biopsy specimens of Barrett's esophagus were taken. Early only the epithelium of the esophagus was studied, but there was no evidence of a propria of the mucous membrane and lymphoid tissue.
Citation Format: Bakhtiyar Talgatuly Azhken. Morphologic consequences for noncapsular lymphoid tissue in the case of malignancy of GERD (Barrett's esophagus) [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B144.
Abstract B148: Microvilli enable efficient T-cell antigen search and ligand detection
Authors: Cai En , Marchuk Kyle , Beppler Casey , Krummel Matthew 
Published: February 2019

Abstract
During antigen detection, T-cells survey the surface of antigen-presenting cells (APCs), which may display mainly nonstimulatory peptide-loaded major histocompatibility complexes (pMHCs) and only rare cognate antigen in a process involving close (nanometer-scale) membrane apposition. Thus, T-cell must solve a classic trade-off between speed and sensitivity. It has long been supposed that microvilli on T-cells act as sensory organs to enable search, but their strategy has been unknown. We used lattice light-sheet microscopy and quantum dot-enabled synaptic contact mapping microscopy to show how microvilli on the surface of T-cells search opposing cells and surfaces before and during antigen recognition. We uncovered that microvilli on T-cell surfaces dynamically survey the majority of opposing surfaces within one minute through anomalous diffusion. T-cell receptor (TCR) recognition resulted in selective stabilization of receptor-occupied protrusions, which was independent of tyrosine kinase signaling and the actin cytoskeleton. We revealed that TCRs on activated T-cells were nonuniformly distributed on cell membrane: some TCRs were concentrated on microvilli, while other TCRs formed high-density patches on flatter membrane regions. Many microvilli were TCR-occupied, but a small population of microvilli were found not occupied by TCRs. TCR high-density patches moved relative to microvilli. During T-cell-APC interaction, we observed T-cell microvilli projected deep into 3D pockets formed by veil structures on the surface of dendritic cells (DC), and DC membrane also conformed to accommodate T-cell microvilli, which increased the effective close-contact area between T-cell and APC. Such scanning pattern enabled T-cells to efficiently scan more APC surface in given time. This work defines the efficienT-cellular search process against which ligand detection takes place in T-cells.
Citation Format: En Cai, Kyle Marchuk, Casey Beppler, Matthew Krummel. Microvilli enable efficient T-cell antigen search and ligand detection [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B148.
Abstract B152: Generation of monoclonal antibodies against a newly identified target for invasive prostate cancer and their use in the development of an antibody-based targeting therapy
Authors: Biase Anna Di , Regad Tarik , Vadakekolathu Jayakumar , Powe Desmond , Jäck Hans-Martin , Roth Edith 
Published: February 2019

Abstract
In 2013, cancer immunotherapy was selected as the breakthrough of the year by Science’s editors and monoclonal antibody therapy is considered one of its most successful tools. When castration-resistant prostate cancer (PCa) disease progresses and despite androgen deprivation treatment, it typically metastasizes, leading to poor patients’ prognosis and survival. In this case, immunotherapy represents the only chance of treatment. In a previous study carried out by our team on the role of cytoplasmic PML1 in the context of epithelial to mesenchymal transition (EMT) in PCa2, we identified a new promising PCa target for antibody-based therapy. Our target, of which we cannot disclose the name for patenting reasons and that we will further refer to as Protein-X, is a type 1 transmembrane protein that is specifically expressed by PCa cell. Transcriptome profiling obtained using Nanostring technology with a cancer progression panel showed that the knockdown of Protein-X leads to an upregulation of the epithelial EMT marker E-cadherin in PCa cells, suggesting its role in the process. Furthermore, the clinical value of Protein-X as a diagnostic and/or prognostic biomarker of invasive and aggressive PCa, is also being investigated by a histopathologist using immunohistochemistry analysis of Protein-X’s expression on tissue microarrays (TMAs). To develop a monoclonal antibody-based therapy against Protein-X, mouse monoclonal antibodies (mAbs) were generated using hybridoma technology. MAbs-producing hybridomas were sequenced and purified mAbs were tested for their specificity by flow cytometry, immunofluorescence, ELISA and immunoblotting assays. Using in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) reporter assay, we show that the antibodies mediate cell cytotoxicity. This result will be further investigated in vivo using a xenograft mouse model. Future experiments will focus on designing and generating chimeric antigen receptor (CARs) modified adoptive T-cell targeting of Protein-X-expressing tumor cells and bispecific antibodies. In summary, we aim to develop an anti-Protein-X antibody-based therapy against invasive prostate cancer, which will potentially represent a new tool to target aggressive PCa responsible for cancer metastasis and poor prognosis in PCs patients.
Citation Format: Anna Di Biase, Tarik Regad, Jayakumar Vadakekolathu, Desmond Powe, Hans-Martin Jäck, Edith Roth. Generation of monoclonal antibodies against a newly identified target for invasive prostate cancer and their use in the development of an antibody-based targeting therapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B152.
Abstract B154: Differential effects of corticosteroids and anti-TNF on tumor-specific immune responses— Implications for the management of irAEs
Authors: Donia Marco , Borch Troels H. , Radic Haja D. , Chamberlain Christopher , Gokuldass Aishwarya , Svane Inge Marie Stentoft , Draghi Arianna 
Published: February 2019

Abstract
Background: Up to 60% of patients treated with cancer immunotherapy develop severe or life threatening immune-related adverse events (irAEs). Immunosuppression with high doses of corticosteroids or, in refractory cases, with tumor necrosis factor (TNF) antagonists, are the mainstay of treatment for irAEs. It is currently unknown what is the impact of corticosteroids and anti-TNF on the activity of antitumor T-cells. Methods: The influence of clinically relevant doses of dexamethasone (corresponding to an oral dose of 10 to 125 mg prednisolone) and infliximab (anti-TNF) on the activation and killing capacity of tumor-infiltrating lymphocytes (TILs) was tested in vitro. Results: Overall, dexamethasone at low or intermediate/high dose impaired the activation (respectively -46% and -62% in n=8) and tumor-killing ability (respectively -48% and -53% in n=6) of tumor-specific TILs. In contrast, a standard clinical dose of infliximab only had a minor effect on T-cell activation and tumor killing (respectively -20% in n=8 and -10% in n=6). A brief resting following exposure to dexamethasone was sufficient to rescue the in vitro activity of TILs. Conclusions: Clinically relevant doses of infliximab only influenced to a lesser extent the activity of tumor-specific TILs in vitro, whereas even low doses of corticosteroids markedly impaired the antitumor activity of TILs. These data support steroid-sparing strategies and early initiation of anti-TNF for the treatment of irAEs in immuno-oncology.
Citation Format: Marco Donia, Troels H. Borch, Haja D. Radic, Christopher Chamberlain, Aishwarya Gokuldass, Inge Marie Stentoft Svane, Arianna Draghi. Differential effects of corticosteroids and anti-TNF on tumor-specific immune responses— Implications for the management of irAEs [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B154.
Abstract B184: Modulating antigen flow to control immune tolerance
Authors: Ruhland Megan K. , Roberts Edward W. , Krummel Matthew F. 
Published: February 2019

Abstract
The immune system must maintain a delicate balance between activation and tolerance. It is required to quickly respond and eliminate a variety of threats while at the same time remain unresponsive upon encountering normal self-cells or commensal bacteria. We have created a system to track antigen trafficking throughout the immune system and using this system have identified a pathway of antigen flow from peripheral tissues and tumors to the draining lymph node (LN). By tracking antigen from steady-state tissues and tumors, we find that antigen is handled differentially in the LN depending on the inflammatory context in the periphery. During pronounced inflammation, self-antigen shows altered trafficking consistent with that of tumor antigen. Interestingly, using both gut and skin systems, commensal bacteria-derived antigen displayed the unique quality of cell type specific uptake. While each of the various migratory dendritic cell (DC) types were proficient at uptake of self and tumor antigens, only migratory CD11b+ DC and macrophages showed detectable commensal antigen uptake. Additionally, tracking of commensal bacteria-derived antigen within DC showed minimal antigen trafficking to the LN, suggesting different modes of maintaining immune tolerance are at play depending on the antigen source. We find that self-antigen can drain to the LN via migratory DC but is limited from passing to resident DC populations, which appears to prevent robust self-reactive T-cell priming. However, in the case of commensal antigen, the restriction of antigen flow is early in the pathway, thus effectively keeping the LN ignorant of antigen. Identifying the signals that restrict antigen flow in cases of immune tolerance will likely provide insight into how tumor antigen availability affects immune activation. Understanding how self, commensal and tumor antigens are handled by immune cells under various contexts will help inform the development of new targeted immunotherapies that seek to activate or inhibit immune activation in cases of cancer and autoimmunity.
Citation Format: Megan K. Ruhland, Edward W. Roberts, Matthew F. Krummel. Modulating antigen flow to control immune tolerance [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B184.
Abstract B190: WASP-dependent actin protrusions mechanically potentiate killing by cytotoxic T-cells
Authors: Tamzalit Fella , Wang Mitchell S. , Jin Weiyang , Boyko Vitaly , Heddleston John M. , Black Charles T. , Kam Lance C. , Huse Morgan 
Published: February 2019

Abstract
Cytotoxic T Lymphocytes (CTLs) play a central role in immune responses against intracellular pathogens and cancer. Cytotoxic responses are induced by the formation of the immunologic synapse after the recognition of the peptide-major histocompatibility complex by the T-cell receptor. Synapse formation is associated dramatic reorganization of both microtubules and filamentous actin (F-actin) within the T-cell. This promotes the directional secretion of toxic perforin and granzymes into the intercellular space, enhancing both the potency and the specificity of targeT-cell killing. We have previously demonstrated that force exertion by CTLs at the immunologic synapse was strongly correlated with the cytotoxic potential. Indeed, force exertion enhances cytotoxicity by increasing membrane tension on the target cell, which in turn promotes the pore-forming activity of secreted perforin. This correlation between applied force and biochemical responses, which we referr to as mechanopotentiation, raised the prospect that CTLs might use three-dimensional structures at the immunologic synapse to coordinate force exertion and lytic granules secretion. In the present study, we investigated the mechanisms underlying mechanopotentiation in CTLs using a combination of three-dimensional micropatterned stimulatory substrates and high-resolution imaging. Our results revealed that CTLs couple lytic granule release with the formation of highly dynamic F-actin rich protrusions. These protrusions, which are generated by the Wiskott-Aldrich Syndrome protein (WASP) and the Arp2/3 actin nucleation complex, are required for coordinating force exertion with cytolytic secretion allowing efficient killing. Our results provide insight into how cells organize mechanical output and emphasize the importance of studying complex, communicative interfaces in three dimensions.
Citation Format: Fella Tamzalit, Mitchell S. Wang, Weiyang Jin, Vitaly Boyko, John M. Heddleston, Charles T. Black, Lance C. Kam, Morgan Huse. WASP-dependent actin protrusions mechanically potentiate killing by cytotoxic T-cells [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B190.
Abstract IA25: Targeting tumor neoantigens to drive effective tumor immunity
Authors: Wu Catherine J. 
Published: February 2019

Abstract
With the recent availability of novel immunologic agents, priority has shifted to understanding the mechanisms of and predicting responses to each treatment. At the heart of cancer and host immune cell interactions is the tumor antigen and host antigen-specific T cell interaction, with the cytotoxic T cell-cognate antigen interaction forming the mechanistic basis for immune-mediated recognition and the killing of malignant cells. While the search for immunogenic tumor antigens has been the subject of decades-long studies, multiple lines of evidence have convincingly demonstrated tumor neoantigens as an important class of immunogenic tumor antigens. Neoantigens arise from amino acid changes encoded by somatic mutations in the tumor cell and have the potential to bind to and be presented by personal HLA molecules. Using next-generation sequencing approaches, we can now systematically identify mutations leading to amino acid changes that can be potentially recognized immunologically through the implementation of neoantigen discovery pipelines. In recent studies, we have demonstrated that neoantigens can be safely and feasibly targeted to generate customized cancer vaccines. We have been undertaking pilot clinical trials to develop personal cancer vaccines in melanoma and glioblastoma that utilize synthetic long peptides as delivery approach for this therapy. Recent results and new directions will be discussed.
Citation Format: Catherine J. Wu. Targeting tumor neoantigens to drive effective tumor immunity [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr IA25.