bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A219: Using poxvirus to improve immunotherapy for brain glioma
Authors: Tang Bingtao , Schane Claire , Shisler Joanna , Roy Edward 
Published: February 2019

Abstract
Oncolytic viral immunotherapy is a novel approach to cancer treatment. Viruses can directly kill cancer cells, provide antigens to dendritic cells to stimulate a T-cell response, and make cancer cells express genes of immune-enhancing cytokines locally within the tumor microenvironment. We used two types of poxvirus, myxoma virus and vvDD vaccinia virus (double deletion of vaccinia growth factor and thymidine kinase), to deliver IL-15/IL-15Rα gene (a cytokine that boosts the immune system) into brain gliomas. We found that the numbers of NK cells and CD8+ T-cells in the tumor area greatly increased and viable cancer cells substantially decreased after the injection of vvDD-IL15/IL15Rα virus. Vaccination of GARC-1 (a neoantigen for mouse glioma) with CpG and Incomplete Freund’s Adjuvant twice before tumor implantation together with vvDD-IL15/IL15Rα virus, rapamycin and celecoxib treatment after tumor implantation eliminated the gliomas. In order to mimic the clinical situation of treatment beginning after establishment of the tumor, GARC-1 specific CD8+ T-cells were adoptively transferred into tumor-bearing mice; when combined with oncolytic poxvirus (either Myx-IL15/IL15Rα or vvDD-IL15/IL15Rα), rapamycin, and celecoxib, this treatment can also cure gliomas. We already confirmed that IL15/IL15Rα, adoptive transfer of GARC-1 specific T-cells and celecoxib are essential components in this combination treatment. Current studies are evaluating the mechanism and contributions of different components of the treatment.
Citation Format: Bingtao Tang, Claire Schane, Joanna Shisler, Edward Roy. Using poxvirus to improve immunotherapy for brain glioma [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 A219.
Abstract B001: Generation of ImmTACTM molecules: Engineering high-affinity soluble T-cell receptors for the treatment of cancer
Authors: Bombik Izabela , Bortoluzzi Alessio , Mai Nicole , Preston Andrew , Vuidepot Annelise , Jakobsen Bent K. , Liddy Nathaniel 
Published: February 2019

Abstract
Immunotherapeutic strategies are centered on harnessing the human immune system to recognise and destroy cancer cells. At Immunocore, we have developed bi-specific Immune-mobilising monoclonal TCRs Against Cancer (ImmTAC) molecules comprising a soluble TCR fused to an anti-CD3 effector function that redirect T-cells to destroy cancer cells. The TCR-targeting domain overcomes a key limitation of traditional antibody-based therapies by targeting short peptide fragments derived from intracellularly processed proteins presented on the cell surface by human leukocyte antigens (HLAs), offering up to nine-fold more potential targets than are accessible to antibodies. To mediate efficient T-cell-mediated tumor clearance, ImmTAC molecules are engineered to overcome the weak affinities of natural TCRs imposed by thymic selection through a complex multistep engineering process described herein.T-cell clones recognising in-house validated cancer-specific peptides are isolated and affinity-enhanced up to a million fold by introducing mutations to the complementarity determining regions, resulting in picomolar affinity TCRs capable of recognizing exceptionally low numbers of target on the cancer cell surface. The TCR is fused to an anti-CD3 scFv to generate an ImmTAC molecule and is made soluble through the inclusion of a non-native disulphide bond. The efficacy and specificity of the ImmTAC molecule is scrutinized using a range of cellular and molecular assays. The potential application of the ImmTAC platform is exemplified by the expanding portfolio of ImmTAC molecules targeting diverse disease indications. Our lead candidate, IMCgp100, recognizes the melanoma-associated gp100 peptide and is in pivotal trials for the treatment of patients with metastatic uveal melanoma.
Citation Format: Izabela Bombik, Alessio Bortoluzzi, Nicole Mai, Andrew Preston, Annelise Vuidepot, Bent K. Jakobsen, Nathaniel Liddy. Generation of ImmTACTM molecules: Engineering high-affinity soluble T-cell receptors for the treatment of cancer [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 B001.
Abstract B011: Inhibition of G9a reestablishes the MHC class I loss due to EMT in lung cancer cells
Authors: Fukumasu Heidge , Pires Pedro R.L. , Xavier Pedro L.P. 
Published: February 2019

Abstract
The epithelial-to-mesenchymal transition (EMT) is an important phenotype for cancer cells to invade and metastasizes. In addition, cancer cells should escape from the immune system during malignant progression. Here, we aimed to demonstrate the potential of G9a inhibition of EMT in cancer cells and most importantly, the reestablishment of MHC class I expression (MHC-I), one of the important factors associated with the loss of antigenicity of cancer cells. The lung epithelial cancer cell line A549 was cultured under controlled conditions in RPMI culture media supplemented with 10% of bovine fetal serum (BFS), 1% of antibiotics (penicillin and streptomycin), 2% of glutamine in incubator at 37oC and air atmosphere containing 5% of CO2. The tumor growth factor beta (TGFb) exposure for 5 days was used to induce EMT. In addition, another group of A549 cells received TGFb plus the UNC0368 an G9a (a histone methyl transferase) inhibitor for 5 days. Then, cells were evaluated for acquiring mesenchymal cell morphology and MHC-I gene expression (relative quantification). After 5 days, A549 cells exposed to TGFb clearly have gone through EMT by changing their morphology to a fibroblast-like phenotype. Also, the MHC-I gene expression decreased significantly (p=0.0036) after EMT. The G9a inhibitor partially impeded the EMT induced changes in morphology of A549 cells and reestablished the MHC-I gene expression to the control level. In conclusion, G9a inhibition seemed a promising therapeutic target to improve the efficacy of immunotherapies depending on neoantigen expression by cancer cells. However, more studies are necessary and are under way in our laboratory.
Citation Format: Heidge Fukumasu, Pedro R.L. Pires, Pedro L.P. Xavier. Inhibition of G9a reestablishes the MHC class I loss due to EMT in lung cancer 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 B011.
Abstract B014: T-cell Elispot Proficiency Panel 2017/2018: Evaluating routine T-cell Elispot assays
Authors: Haley Stephen T. , Halgreen Charlotte , Frederiksen Katrine , Brogaard Rikke , Brix Liselotte 
Published: February 2019

Abstract
Monitoring antigen-specific T-cell responses is becoming increasingly important in Immunotherapeutic research and development. Thanks to the harmonization efforts by the CIC and CIMT over many years, and the development of better reagents and protocols, MHC multimer and T-cell Elispot assays are now more reliable and accurate assays for monitoring antigen-specific T-cell immunity. Supported by CIMT and CIC, Immudex has conducted a T-cell Elispot proficiency panel Winter 2017/2018 to evaluate assay performance in immune monitoring laboratories routinely doing T-cell Elispot assays. 39 worldwide participants received two cell samples, together representing low, medium and high responses for two predefined peptide pools. A negative control reagent was also included. Participants were asked to use the Direct Human IFNγ Elispot Assay to determine spot count corresponding to each of the predefined peptide pools and the negative control reagent. After performing the Direct Human IFNγ Elispot Assay, the participants report back their results for each cell sample as “number of spots per 200.000 viable cells” for each of the predefined peptide pools and negative control reagent. The data set was analyzed, and each participating laboratory received a report detailing the individual laboratory’s performance (in an anonymized format). The anonymized report was publicly available April 2018, and data will be presented at the CRI-CIMT-EATI-AACR Fourth International Cancer Immunotherapy Conference.
Citation Format: Stephen T. Haley, Charlotte Halgreen, Katrine Frederiksen, Rikke Brogaard, Liselotte Brix. T-cell Elispot Proficiency Panel 2017/2018: Evaluating routine T-cell Elispot assays [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 B014.
Abstract B030: Predicting the response of uveal melanoma to immunotherapy with MRI assessments
Authors: Moreira Alvaro , Saake Marc , Schuler Gerold , Heinzerling Lucie 
Published: February 2019

Abstract
Purpose: Contrary to cutaneous melanoma, uveal melanoma is little responsive to immune checkpoint inhibitors. This is thought to result from a different immunogenicity of these two melanoma variants. We sought to investigate whether imaging properties in magnetic resonance imaging (MRI) were able to predict the response of liver metastases of uveal melanoma to immune checkpoint blockade. Study Design: Pre- and post-therapeutic liver MRIs, including a native T1-weighted fat-saturated FLASH sequence, were analyzed in a population of patients with uveal melanoma, segmenting the metastasis into areas of active tumor, necrosis and edema. Different lesions from all of the patients were investigated and their patterns correlated with response to immunotherapy. Results: Contrary to previous results of other research groups, MRI signal intensity scores in our population could not predict response to immunotherapy. Therefore, we could not validate the MRI assessment as a clinical biomarker. Other parameters need to be integrated in the radiomic signature. Conclusions: Current MRI imaging methods are limited in their ability to predict response of liver metastases of uveal melanoma to immune checkpoint blockade. Advanced MRI imaging methods, more sensitized to different biophysical processes including blood perfusion and tumor metabolism, which can provide more specific information on tissue physiology, should be investigated in the light of emerging immunotherapies for uveal melanoma, such as tumor-infiltrating lymphocytes and recent developments in dendritic cell cancer vaccines.
Citation Format: Alvaro Moreira, Marc Saake, Gerold Schuler, Lucie Heinzerling. Predicting the response of uveal melanoma to immunotherapy with MRI assessments [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 B030.
Abstract B033: T-cell-induced tumor vulnerability discovery in an IFNγ-independent genomic landscape
Authors: Peeper Daniel S. , Vredevoogd David , Kuilman Thomas 
Published: February 2019

Abstract
New clinical opportunities are needed to increase immunotherapy (IT) benefit. Whereas IFNγ-pathway mutations cause IT resistance, we find that IFNγ receptor-deficient tumors remain remarkably susceptible to T-cell elimination. By integrating transcriptomics, proteomics and genome-wide CRISPR-Cas9 screening with clinical data, we defined the IFNγ-independent tumor landscape and uncovered an immunotherapeutic opportunity. Ablation of TRAF2 enhanced T-cell elimination of both melanoma and lung cancer cells by redirecting TNF signaling to favor RIPK1-dependent apoptosis. TRAF2 loss greatly enhanced the therapeutic potential of pharmacologic inhibition of its interaction partner cIAP. Corroborating these observations clinically, we identified recurring TRAF2 mutations that reduced T-cell sensitivity of tumor cells. Furthermore, both IT response duration and overall survival were lower for tumors that had acquired TNF pathway mutations on IT, suggesting immune-editing by TNF pressure. These results functionally annotate the tumor genome landscape of IFNγ-independent T-cell cytotoxicity, and merit clinical exploration of TRAF2 for cancer immunotherapy.
Citation Format: Daniel S. Peeper, David Vredevoogd, Thomas Kuilman. T-cell-induced tumor vulnerability discovery in an IFNγ-independent genomic landscape [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 B033.
Abstract B040: Electrospun implantable anticancer device comprising immune adjuvant photo-responsive nanoparticles with checkpoint blockade for effective cancer therapy
Authors: Unnithan Afeesh Rajan , Sasikala Arathyram Ramachandra Kururp , Park Chan Hee , Kim Cheol Sang 
Published: February 2019

Abstract
An implantable anticancer device (IAD) that can eradicate local regional breast cancer recurrence (LRR), inhibit metastasis as well as to enhance the breast reconstruction during/after therapy is proposed. The IAD is developed by combining nanofiber-based chemo-photothermal therapy platform with check point blockade immunotherapy. Here we developed a coreshell electrospun nanofiber encapsulated with drug conjugated MoS2 as chemo-photothermal agent along with imiquimod as an immune response modifier. The near-infrared laser exposure to IADs can generate tumor-associated antigens from primary tumors, which in the presence of released imiquimod from IADs can show vaccine-like functions. Moreover, the nanofiber matrix will enable the sustained and tumor-specific anticancer drug release with a minimum initial burst release and the repeated photothermal capability to ensure the synergistic inhibition of tumor recurrence. In addition to that, the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4) in combination with the generated immunologic responses will be able to attack remaining tumor cells causing metastasis inhibition with strong immunologic memory effect, which can shield against the tumor recurrence after the post elimination of initial tumors. The IAD nanofiber morphology resembles the extra cellular matrix (ECM) enrich the reconstruction of poor breast cosmesis resulted from the surgical treatment, by supporting the lipofilling of the surgical residual cavity to induce the adipogenic process. So, in this work we propose that the tumor associated antigens created in situ after photothermal therapy by the immune adjuvant nanofiber IAD could show vaccine-like functions, which in combination with checkpoint blockade show strong antitumor immune responses for effective cancer immunotherapy as a potential platform for synergistic inhibition of LRR and a great promise for the in situ breast reconstruction ability for better breast cosmesis.
Citation Format: Afeesh Rajan Unnithan, Arathyram Ramachandra Kururp Sasikala, Chan Hee Park, Cheol Sang Kim. Electrospun implantable anticancer device comprising immune adjuvant photo-responsive nanoparticles with checkpoint blockade for effective cancer 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 B040.
Abstract B043: Enhanced T-cell immunity in vivo using injectable bioengineered scaffolds
Authors: Shah Nisarg , Mooney David J. 
Published: February 2019

Abstract
Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for hematological malignancies and immunologic disorders, but allogeneic HSCT is limited by deficiency and dysregulation of T-cells. We aimed to enhance post-HSCT T-cell reconstitution and hypothesized that a T-cell lymphopoietic bone marrow niche might be engineered to foster production of T-cell progenitors in vivo, which can undergo host-driven selection. To test this hypothesis, we created an injectable biomaterial-based scaffold that promotes T-cell development in vivo by recapitulating key features of the bone marrow niche. The composite device, referred to as a bone marrow cryogel (BMC), is comprised of a macroporous hydrogel-based scaffold permitting cellular infiltration. The presentation of T-lineage cues in a bone marrow-like microenvironment enhanced thymic seeding of progenitors and facilitated the enhancement of donor T-cell reconstitution after HSCT in mice. The BMC-reconstituted T-cells were functional, with a diverse T-cell receptor repertoire and modulated GVHD. BMC may represent a simple to administer, off-the-shelf approach to post-HSCT T-cell regeneration.
Citation Format: Nisarg Shah, David J. Mooney. Enhanced T-cell immunity in vivo using injectable bioengineered scaffolds [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 B043.
Abstract B052: Immunotherapy for melanoma by adenovirus-mediated full-length antibody, nivolumab
Authors: Wang Xuchen 
Published: February 2019

Abstract
Nivolumab, a fully human, IgG4 immune checkpoint inhibitor antibody, binds PD-1 on activated immune cells to disrupt PD-1 interaction with PD-L1 and PD-L2 ligands, thereby attenuating inhibitory signals and augmenting the host antitumour response. In 2014, nivolumab was approved by FDA and has been used to treat various types of cancer such as melanoma, non-small cell lung cancer, renal cell carcinoma, and classic Hodgkin's lymphoma. However, due to the high price of nivolumab and the long cycle of treatment, many patients cannot afford and receive adequate treatment. Here, we generated a new, cheaper form of nivolumab for cancer immunotherapy, by cloning the full-length nivolumab antibody gene into two serotypes of adenovirus vectors, termed as AdHu5-Nivo and AdC68-Nivo. Ad vectors based on human serotype 5 (AdHu5) have been proved in a lot of previous studies to be safe and efficient. Compared with AdHu5, chimpanzee Ads exhibit much lower seroprevalence in human beings, which made them great alternative Ad gene vector. Until now, we have detected a high expression of nivolumab in vitro by Western blot and sandwich ELISA. In vivo studies showed that a single dose of AdHu5-Nivo or AdC68-Nivo can induce sustained nivolumab expression. The biologic activities of the two mAbs are analogous compared with commercial monoclonal antibody. To follow up we will verify their antitumor effects on both cellular level and melanoma transplant animal models.
Citation Format: Xuchen Wang. Immunotherapy for melanoma by adenovirus-mediated full-length antibody, nivolumab [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 B052.
Abstract B058: Rapid and controlled T-cell expansion using scaffolds that mimic antigen-presenting cells
Authors: Zhang David K.Y. , Vaynrub Anna , Mooney David J. 
Published: February 2019

Abstract
Current approaches to expand T-cells ex vivo for therapeutic applications are limited by low expansion rates and often result in unpredictable expansion products of varying phenotype and function. Key attributes, such as a balanced ratio of CD4-to-CD8 T-cells, or a high central memory T-cell fraction are known to correlate with robust and durable therapeutic responses but remain difficult to reproducibly achieve. Strategies that allow one to precisely control the phenotype of expanded T-cell products may thus potentiate the effects of CAR-T-cell therapies, and understanding how T-cells respond to stimulation is a crucial step to this end. Recently, we described a 3D expansion system that mimics natural antigen presenting cells (APCs) and promotes greater polyclonal expansion of primary human T-cells than commercial expansion beads (Dynabeads). These biodegradable, APC-mimetic scaffolds (APC-ms) are composed of fluid lipid bilayers supported on mesoporous silica micro-rods, which enables precise control over the spatial organization of membrane-bound T-cell receptor (TCR) stimulatory and costimulatory cues (i.e., anti-CD3/anti-CD28). Here, we investigated the activation and memory signature of primary human T-cells over time in response to APC-ms with different densities of activating surface cues compared to Dynabead stimulation. Higher surface cue densities of anti-CD3/anti-CD28 promoted greater proportions of central memory T-cells, with a parallel increase in the CD4-to-CD8 T-cell ratio. T-cells stimulated with Dynabeads exhibited higher expression of CD25 and CD69 that peaked earlier than standard APC-ms formulations, suggesting that APC-ms promotes relatively more transient T-cell activation than Dynabeads, potentially mitigating overstimulation and exhaustion. Overall, these data demonstrate that APC-ms can be used to rapidly expand primary human T-cells and tune their phenotypic attributes (e.g., CD4-to-CD8 ratio and memory subpopulations). This technology has the potential to improve the production of T-cells for adoptive T-cell-based therapies.
Citation Format: David K.Y. Zhang, Anna Vaynrub, David J. Mooney. Rapid and controlled T-cell expansion using scaffolds that mimic antigen-presenting 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 B058.