bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B036: T-cell recognition of breast cancer antigens
Authors: Petersen Nadia Viborg , Ramskov Sofie , Andersen Rikke Sick , Met Özcan , Straten Per thor , Bentzen Amalie Kai Kai , Hadrup Sine Reker 
Published: February 2019

Abstract
Breast cancer remains the leading cause of cancer death among women worldwide, rendering conventional therapies insufficient despite decades of research. Despite originally considered an immunologically silent malignancy, recent studies have shown encouraging results, from treatment of breast cancer with checkpoint inhibition to enhance the immunogenicity and tumor cell killing mediated by immune cells. The epitope landscape in breast cancer is minimally described; thus it is necessary to identify T-cell targets to develop cancer-specific immune-mediated therapies. This project investigates four proteins commonly upregulated in breast cancer and thus probable tumor-associated antigens (TAAs), namely, aromatase, prolactin, never in mitosis a related kinase 3 (NEK3), and protein inhibitor of activated STAT3 (PIAS3). Each contributes to increase growth, survival, and motility of malignant cells. To uncover novel epitopes for cytotoxic T-cells, a reverse immunology approach is applied. In silico screening via NetMHC was used to predict peptides within the full length of each of the four proteins that bind to HLA-A*0201 and HLA-B*0702. Via in silico screening 415 HLA-A*0201 or HLA-B*0702 binding peptides were predicted An MHC ELISA was applied to experimentally confirm which of the peptides are true HLA-A*0201 and HLA-B*0702 binders, reducing the library from 415 to 147. The 147 peptides were evaluated for T-cell recognition utilizing DNA barcode labeled MHC multimers to screen peripheral blood lymphocytes from 24 breast cancer patients and 18 healthy donor samples. Significantly more TAA specific T-cell responses were detected in breast cancer patients than healthy donors for both HLA-A*0201 (p=0.0039) and HLA-B*0702 (p&lt;0.001) restricted peptides. Thus, the inspected proteins aromatase, prolactin, NEK3 and PIAS3 indeed contain targets for T-cell reactivity. Importantly, several of the responses were identified towards peptides with a predicted intermediate HLA-binding affinity. This emphasizes the importance of including such weaker affinity ligands in the search for epitopes within shared TAAs.
Citation Format: Nadia Viborg Petersen, Sofie Ramskov, Rikke Sick Andersen, Özcan Met, Per thor Straten, Amalie Kai Kai Bentzen, Sine Reker Hadrup. T-cell recognition of breast cancer antigens [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 B036.
Abstract B041: An injectable magnetic nanogel system for filling surgical residual cavity with effective cancer immunotherapy combined hyperthermic capability
Authors: Sasikala Arathyram Ramachandra Kururp , Unnithan Afeesh Rajan , Park Chan Hee , Kim Cheol Sang 
Published: February 2019

Abstract
The advancement in nanotechnology has created a wealth of new possibilities for treating cancer with multifunctional nanosystem holding various therapeutic strategies in a single platform. It has been reported that magnetic nanoparticle hyperthermia can induce antitumor immunity whereas the immunotherapy can naturally trigger the immune system with the help of an appropriate stimulator to control cancer. Therefore the present study investigates the effectiveness of a hybrid nanocomposite system to effectively exterminating the tumor associated immune cells (TICs) as well as inducing an inflammatory immune response by activating killer T-cells by combining magnetic hyperthermia with an immunostimulatory agent. Here we report an injectable magnetic nanogels conjugating a checkpoint inhibitor (T-lymphocyte antigen-4 [CTLA4]) and a Toll-like receptor (TLR) agonists (imiquimod) for generating an effective antitumoral immune response for postsurgical glioma treatment. The injectable conductive magnetic hydrogel system enables the tracing and deterring of the recurrent tumor cells via magnetic nanoparticle-mediated hyperthermia with the strong immunologic memory effect. The superparamagnetic iron oxide nanoparticles encapsulated nanogels exhibit an induced heating ability in an alternating magnetic field (AMF) and thereby trigger the tumor cells to undergo a burst release of heat shock proteins to recruit immune cells to generate tumor-allied antigens. These antigens along with the released imiquimod from the hydrogel can generate vaccine-like functionalities. Moreover, the introduction of anti-cytotoxic T-lymphocyte antigen-4 (CTLA4) as a checkpoint-blockade will generate memory T-cells, which in turn will attack the metastatic and recurrent tumor cells. Above all, the conductive bioactive scaffold will support the neuronal regeneration and reactivation of brain cells. Thus our multifunctional novel hydrogel system will be able to fill the surgical residual cavity to prevent the glioma recurrence and will improve the local neuronal tissue reconstruction along with hyperthermic-immunotherapy.
Citation Format: Arathyram Ramachandra Kururp Sasikala, Afeesh Rajan Unnithan, Chan Hee Park, Cheol Sang Kim. An injectable magnetic nanogel system for filling surgical residual cavity with effective cancer immunotherapy combined hyperthermic capability [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 B041.
Abstract B053: In vivo metabolic labeling and targeted modulation of dendritic cells for enhanced cancer immunotherapy
Authors: Wang Hua , Mooney David J. 
Published: February 2019

Abstract
Targeted immunomodulation of dendritic cells (DCs) is critical for optimizing antigen presentation processes and amplifying anticancer immune responses, but a general strategy has been lacking thus far. Here we show that the subcutaneously injected pore-forming alginate gels loaded with GM-CSF and azido-sugar nanoparticles can recruit and metabolically label DCs with azido groups in vivo, which allows for tracking and targeted modulation of DCs that migrate out of the gel scaffolds. Azido-labeled DCs were detected in both the gels and draining lymph nodes and enabled targeted delivery of dibenzocyclooctyne (DBCO)-bearing antigens and adjuvants via efficient Click chemistry, resulting in a higher level of antigen-specific CD8+ T-cells and better antitumor efficacy in comparison to unmodified antigens and adjuvants. We further show that azido-labeled DCs enable surface display of DBCO-cytokines, IL2 and IL15/IL15R for example, for targeted modulation of effector T-cells, which provides a general strategy to manipulate DCs and DC-T-cell interaction in vivo and opens a new avenue for developing enhanced cancer immunotherapy.
Citation Format: Hua Wang, David J. Mooney. In vivo metabolic labeling and targeted modulation of dendritic cells for enhanced 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 B053.
Abstract B073: A pan-HLA predictor of neoantigen processing and presentation to the tumor cell surface
Authors: Clancy Trevor , Stratford Richard 
Published: February 2019

Abstract
Currently, neoantigens are often predicted using algorithms predominantly based on knowledge of the key peptide binding affinity difference between HLA alleles. Although HLA binding algorithms predict binding affinity of a peptide to HLA reasonably well, they do not predict processing and presentation of to the cell surface (i.e., the immunopeptidome). In fact, only 15%–20% of “predicted” peptide binders are processed or presented, and therefore contribute to the immunopeptidome. Erroneous predictions may be addressed with time-consuming and laborious experiments, such as mass-spectrometry (MS). However, in silico predictions may also prove to be very useful in prioritizing therapeutically relevant immunogenic peptides. Previous in silico studies that predict naturally processed and presented peptides to the cell surface have focused on only one of the many steps in the antigen processing and presentation pathway (such as TAP transport or proteasome cleavage, etc.). Additionally, previous antigen processing prediction tools have been trained and are therefore applicable to specific HLA alleles, making it challenging to make predictions for not so well-characterized alleles. Here, we outline a machine learning approach trained on MS elution data that predicts, in a pan-HLA manner, natural processing and presentation of neoantigens to the cell surface. The predictor is integrated with multiple immune parameters in a deep learning layer to predict neoantigens, and may be used for more accurate neoantigen predictions for any HLA allele, in both the class I and class II systems. Further, by analyzing previously published clinical data we illustrate that its application leads to a significantly improved identification of neoantigen targets for personalized cancer immunotherapy.
Citation Format: Trevor Clancy, Richard Stratford. A pan-HLA predictor of neoantigen processing and presentation to the tumor cell surface [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 B073.
Abstract B084: Methylation landscape of tumors associated with antitumor immune signature
Authors: Ock Chan-Young , Park Changhee , Jeong Kyeonghun , Jung Sohee , Bae Jeong Mo , Kim Kwangsoo 
Published: February 2019

Abstract
The most reliable predictive biomarker of cancer immunotherapy is gene expression profile (GEP) of tumor microenvironment. GEPs such as local immune cytolytic activity, interferon-gamma signature, and immune signature score have been reported to represent anti-tumor immune signature. Previously, we reported that immune signature score was positively correlated with tumor mutational burden, but negatively correlated with chromosomal instability (CIN) score, since tumors with high CIN score had significantly low neoantigen burden. However, methylation signature or burden of tumor would also affect antitumor immunogenicity, there has been no analysis reported so far. In the current study, we investigated if methylation landscape of tumor would be associated with GEPs of anti-tumor immune signature using The Cancer Genome Atlas (TCGA) pan-cancer database. In TCGA, 8269 pan-cancer samples had both RNA sequencing data and methylation data using Infinium HumanMethylation450K BeadChip, which were included in the main analysis. Although tumors with high mutational burden (Mu-type) and high CIN burden (C-type) were exclusively classified with negative correlation, methylation burden was not correlated with mutational burden or CIN burden in any pattern. Interestingly, antitumor immune signature measured by local immune cytolytic activity (CytAct) was clearly decreased with high methylational burden, as seen in high CIN burden. Hypermethylation of promoter of genes related to tumor antigen recognition by T-cell such as HLA family, B2M, CD74, and CD274 (PD-L1) were negatively associated with CytAct in pan-cancer analysis. In conclusion, methylation signature of tumor is also associated with antitumor immunogenicity with a negative correlation in general. Further study of whether specific methylation pattern would be associated with anti-PD-1/PD-L1 inhibitors in clinical study would be warranted.
Citation Format: Chan-Young Ock, Changhee Park, Kyeonghun Jeong, Sohee Jung, Jeong Mo Bae, Kwangsoo Kim. Methylation landscape of tumors associated with antitumor immune signature [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 B084.
Abstract B099: Elucidating the mechanisms that underpin RAG chromatin scanning in V(D)J recombination at antigen receptor gene loci
Authors: Ba Zhaoqing , Jain Suvi , Hu Jiazhi , Alt Frederick 
Published: February 2019

Abstract
Immunoglobulin heavy (IgH) and light (IgL) chain variable region exons are assembled from V, D and J segments by V(D)J recombination, which is initiated by RAG1/RAG2 endonuclease (RAG) that introduces DNA double-stranded breaks (DSBs) between a pair of V, D, and J coding segments and flanking recombination signal sequences (RSSs). IgH V(D)J recombination is ordered, with D-JH joining occurring before appendage of a VH to a DJH intermediate in pro-B cells. In pre-B cells, a single-step VL-to-JL recombination event is invoked at IgL loci, with Ig kappa rearrangement usually preceding that of Ig lambda. The mechanisms of Ig V(D)J recombination, especially long-range VH-to-DJH and Vkappa-to-Jkappa recombination are still not fully understood. Recently, our work showed CTCF-binding elements (CBEs) immediately downstream of frequently rearranged VH-RSSs increase recombination potential of their associated VH far beyond that provided by RSS alone. This CBE activity becomes particularly striking upon the inactivation of IgH IGCR1 control element, which promotes DJH intermediate formation by insulting Ds, JHs, and recombination center (RC) from upstream VHs in a CBE-anchored chromatin loop. By developing and applying 3C-HTGTS, a new high-throughput chromosome conformation capture method that shows great advantages over classical 4C-seq in sensitivity and specificity, we found VH-associated CBEs promotes interaction with the RC. Based on these, we proposed a RAG chromatin scanning model for V(D)J recombination, in which VH CBEs stabilize interactions of D-proximal VHs first encountered by the DJH RC during linear RAG scanning on chromatin and thereby promote dominant rearrangement of these VHs by an unanticipated chromatin accessibility-enhancing CBE function. However, it is still not known if such chromatin scanning also happens on other antigen receptor loci and what the underlying mechanism is. Here, we will show our new findings on the roles of RAG chromatin scanning in Vkappa-to-Jkappa recombination at Ig kappa locus by multiple comprehensive approaches. Moreover, we will also discuss our most updated understanding of the mechanisms underlying RAG chromatin scanning using a novel and sophisticated approach. The potent mutagenic and oncogenic effects of aberrant RAG chromatin scanning at RAG “off-target” sites genome-wide will be also discussed.
Citation Format: Zhaoqing Ba, Suvi Jain, Jiazhi Hu, Frederick Alt. Elucidating the mechanisms that underpin RAG chromatin scanning in V(D)J recombination at antigen receptor gene loci [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 B099.
Abstract B107: Next generation of poxvirus-based immunotherapeutics
Authors: Fend Laetitia 
Published: February 2019

Abstract
Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles. We report here that a VACV can induce immunogenic cell death and generate a systemic immune response. Effects on tumor growth and survival was largely driven by CD8 T-cells, and immune cell infiltrate in the tumor could be reprogrammed toward a higher ratio of effector CD8 T-cells to regulatory CD4 T-cells. We demonstrate also the successful vectorization of a monoclonal anti-mPD-1 antibody in our VACV. The vectorized anti-mPD-1 antibody was able to block the binding of mPD-1 ligand to mPD-1 in vitro. Moreover, mAb was detected in tumor and in serum of C57BL/6 mice when the recombinant VACV was injected intratumorally (i.t.) in B16F10 and MCA 205 tumors. The concentration of circulating mAb detected after i.t. injection was up to 1,900-fold higher than the level obtained after a subcutaneous (s.c.) injection (i.e., without tumor), confirming the virus tropism for tumoral cells. Moreover, the overall tumoral accumulation of the mAb was higher and lasted longer after i.t. injection of the recombinant VACV than after i.t. administration of 10 µg of anti-mPD1. Interestingly, in the MCA 205 tumor model, the antitumoral activity of the VACV expressing mPD-1 is similar to the therapeutic efficacy of the combination of the unarmed VACV combined with a systemically administration of an anti-mPD-1 antibody and superior to that obtained with the unarmed VACV alone. These results pave the way for next generation of OV armed with immunomodulatory therapeutic molecules.
Citation Format: Laetitia Fend. Next generation of poxvirus-based immunotherapeutics [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 B107.
Abstract B126: Degradation-regulatable architectured implantable macroporous scaffold for the spatiotemporal modulation of immunosuppressive microenvironment and enhanced combination cancer immunotherapy
Authors: Ren Long , Shin Il Woo , Song Chanyoung , Lim Yong Taik 
Published: February 2019

Abstract
The presence of immunosuppressive cells such as tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) in residual tumors after surgery is known to be related to high recurrence of tumors which are more resistant to therapeutic interventions compared with the primary ones. Herein, a degradation-regulatable architectured implantable macroporous scaffold (Dr-AIMS) is designed to act as a local drug delivery reservoir, modulating the immunosuppressive tumor microenvironment (TME) and activating T-cell-based antitumor immunity as well. The Dr-AIMS is fabricated by the crosslink of methacrylate-modified hyauronic acid under frozen state to form the interconnected macroprorous architacture with pore size of 252.36 ± 59.57 μm. By combining stable “bulk” material (methacrylate-modified hyaluronic acid) and hydrolytic-labile “sacrificing” component (methacrylate-modified oxidized hyaluronic acid) with varied blending ratios, the degradation can be regulated with 10-28 days after implantation in mice. In vitro results indicated that PTX could induce immunogenic 4T1 cell death and deplete TAMs, and R837 could activate antigen presenting cells and inhibit MDSCs functions. After loading PTX, R837 and combined immune checkpoint blockade molecules (anti-CTLA-4 and anti-OX40 mAbs, invigorating T-cells function), Dr-AIMS was implanted as postsurgical treatment (~10% remaining) in 4T1 breast tumor model. In vivo results suggested that the generation of systemic anti-tumor immunity required continuous drug supplies for at least two weeks. The sustained and localized supply of immunomodulatory drugs from Dr-AIMS facilitated the depletion of MDSCs and M2-like macrophages simultaneously within the tumor tissues, converting immunosuppressive TME into antitumor immunity niches. Also, enhanced infiltration of DCs and effector T-cells into tumor was observed, and systemic antitumor immunity was generated with 10-fold reduced doses, resulting in the prolonged survival of mice after surgery of incompletely removed tumor.
Citation Format: Long Ren, Il Woo Shin, Chanyoung Song, Yong Taik Lim. Degradation-regulatable architectured implantable macroporous scaffold for the spatiotemporal modulation of immunosuppressive microenvironment and enhanced combination 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 B126.
Abstract B133: Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor immunity
Authors: Song Chanyoung , Shin Il Woo , Ren Long , Lim Yong Taik 
Published: February 2019

Abstract
The development of biomaterial-based immune niches that can shape tumor-induced immunosuppressive factors will play an important role to improve current cancer immunotherapy. Herein, we developed an engineered 3-dimensional porous scaffold for creating synergistic action between myeloid-derived suppressor cell (MDSC)-depleting drugs, which can revert an immunosuppressive tumor microenvironment to one supporting antitumor immunity, and cancer vaccines (whole tumor lysate-based antigens and nano-adjuvants carrying Toll-like receptor 3 agonists), which can induce tumor antigen-specific T-cell responses. The local implantation of the scaffold (called immuneCare-DISC, iCD) as a post-surgical treatment in large established 4T1 breast tumors induced systemic antitumor immunity and prevented relapse and metastasis, resulting in survival of 100%. These therapeutic results were obtained from the depletion of MDSCs by control releasing of gemcitabine and the recruitment/activation of dendritic cells, increased infiltrating of T-cells and enhanced level of IFN-γ production by sustained releasing of cancer vaccine from the iCD. This synthetic immune niche iCD as a spatiotemporal modulation of tumor-induced immunosuppression and cancer vaccine-induced immune stimulation is proposed to generate favorable environment to prevent recurrence and metastasis following the surgical resection.
Citation Format: Chanyoung Song, Il Woo Shin, Long Ren, Yong Taik Lim. Implantable synthetic immune hydrogel for spatiotemporal modulation of tumor-derived immunosuppression and systemic antitumor 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 B133.