bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A28: Generation and characterization of anti-idiotype antibody ganglidiomab as GD2 surrogate for immunotherapy of neuroblastoma.
Authors: Lode Holger N. , Schmidt Manuela , Seidel Diana , Huebener Nicole , Brackrock Diana , Bleeke Matthias , Reker Daniel , Brandt Sven , Mueller Hans-Peter , Helm Christiane , Siebert Nikolai 
Published: August 2014

Abstract
Purpose: Immunotherapy targeting disialoganglioside GD2 emerges as an important treatment option for neuroblastoma, a pediatric malignancy characterized by poor outcome. Here, we report the generation and characterization of ganglidiomab, a new anti-idiotype antibody to anti-GD2 antibodies of the 14.18 family for monitoring of clinical trials and the development of neuroblastoma vaccines.
Experimental Design and Results: Balb/c mice were immunized with 14G2a and splenocytes harvested to generate hybridoma cells. Clones were screened by ELISA for mouse antibody binding to hu14.18. One positive clone was selected to purify and characterize the secreted IgG protein (κ, IgG1). This antibody bound to anti-GD2 antibodies 14G2a, ch14.18/CHO, hu14.18 and to immunocytokines ch14.18-IL2 and hu14.18-IL2 as well as to NK-92 cells expressing scFv(ch14.18)-zeta receptor. Binding of these anti-GD2 antibodies to the nominal antigen GD2 as well as GD2 specific lysis of neuroblastoma cells by NK-92-scFv(ch14.18)-zeta cells was competitively inhibited by ganglidiomab, proving GD2 surrogate function and anti-idiotype characteristics. The dissociation constants of ganglidiomab from anti-GD2 antibodies ranged from 10.8 ± 5.01 to 53.5 ± 1.92 nM as determined by Biacore analyses using “steady state” analysis. The sequences of framework- (FRs) and complementarity determining -regions (CDRs) of ganglidiomab were identified. Finally, we demonstrate induction of a GD2 specific humoral immune response after vaccination of mice with ganglidiomab effective in mediating GD2 specific killing of neuroblastoma cells.
Conclusion: We generated and characterized a novel anti-idiotype antibody ganglidiomab for immune monitoring of clinical trials with anti-GD2 antibodies and provide an important baseline for the development of anti-idiotype vaccines against malignancies expressing GD2.
Citation Format: Holger N. Lode, Manuela Schmidt, Diana Seidel, Nicole Huebener, Diana Brackrock, Matthias Bleeke, Daniel Reker, Sven Brandt, Hans-Peter Mueller, Christiane Helm, Nikolai Siebert. Generation and characterization of anti-idiotype antibody ganglidiomab as GD2 surrogate for immunotherapy of neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A28.
Abstract A53: Alpha particles and induction of an antitumor immune response.
Authors: Gorin Jean-Baptiste , Gouard Sébastien , Chérel Michel , Faivre-Chauvet Alain , Ménager Jérémie , Morgenstern Alfred , Bruchertseifer Frank , Davodeau François , Gaschet Joëlle 
Published: August 2014

Abstract
Objectives: Radioimmunotherapy (RIT) is an approach allowing targeting of radioelements to tumours, usually through the use of antibodies specific for tumour antigens. The radiations emitted by the radioelements then induce direct killing of the targeted cells as well as indirect killing through bystander effect. Interestingly, it has been shown that ionizing radiation, in some settings of external radiotherapy, can foster an immune response directed against tumour cells. Our research team is dedicated to the development of alpha RIT, i.e RIT using alpha particle emitters, we therefore decided to study the effects of such particles on tumour cells in regards to their immunogenicity.
Material and Methods: We studied the effects of bismuth-213, an alpha emitter, on cellular death and autophagy in a mouse (5T33) and a human (LP-1) myeloma cell line. Using flow cytometry analysis, we measured the expression of MHC molecules and several DAMPs at the cell surface to determine whether irradiation with bismuth-213 could cause the tumour cells to be recognized by the immune system. We also tested the irradiated cell culture media by ELISA to check whether DAMPs were secreted after treatment with bismuth-213. Finally, a co-culture of dendritic cells with irradiated tumour cells or their culture media was performed to test whether it would induce dendritic cell activation.
Results: Only slight levels of apoptosis and necrosis were detected within the 48 hours following irradiation in the studied cell lines, however they both exhibited signs of autophagy. No increase in membrane or extracellular expression of DAMPs was observed after treatment with bismuth-213, or in the expression of MHC class I and II. However, the co-culture experiments indicated that soluble factors are released in the culture media after irradiation with bismuth-213, which are able to induce dendritic cell activation.
Conclusion: These data suggest that alpha particles would be of interest in rising an immune response associated to RIT.
Citation Format: Jean-Baptiste Gorin, Sébastien Gouard, Michel Chérel, Alain Faivre-Chauvet, Jérémie Ménager, Alfred Morgenstern, Frank Bruchertseifer, François Davodeau, Joëlle Gaschet. Alpha particles and induction of an antitumor immune response. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A53.
Abstract A56: The number of MDSC (Gr1+/CD11b+) and T lymphocytes in blood of canine patients during mammary and skin tumors development.
Authors: Mucha Joanna , Homa Agata , Majchrzak Kinga , Motyl Tomasz , Król Magdalena 
Published: August 2014

Abstract
The very recent studies have indicated an important role of myeloid derived suppressor cells (MDSC) in the tumor progression and metastasis. They are thought to suppress the immune system and promote angiogenesis via STAT3 activation.
The aim of present study was two-fold: 1) to assess the percentage of MDSCs (CD11b+/Gr1+) in canine blood leukocytes and percentage of MDSCs that express p-STAT3 at high level; and 2) to assess the percentage of CD3+, CD4+, CD8+ and Treg (CD4+/FoxP3+) in canine blood lymphocytes collected from patients with various clinical stage of mammary and skin tumors comparing to control healthy dogs. The samples were analyzed using BD FACS AriaII.
The results of our study indicate that percentage of Gr1-positive cells is significantly increased (p&lt;0.05) in patients with stage IV tumor (4.6%, compared to control and stage I, II and III tumor: 2.38%, 0.8%, 0.65%, 1.2%, respectively). The number of Treg cells was significantly decreased (p&lt;0.001) in patients with stage III and IV tumor (1.06% and 1.03%, respectively) compared to control (4.82%), stage I and II tumor (6.5% and 3.95%, respectively). Similarly, the number of CD4+ cells was significantly decreased (p&lt;0.01 and p&lt;0.001) in stage III and IV tumors (14.8% and 2.27%, respectively) compared to control (29.84%), and stage I and II tumors (26.20% and 18.75%, respectively). Thus, the ratio of CD4/CD8 was also significantly decreased (p&lt;0.01 and p&lt;0.001) in stage III and IV tumors (respectively). The number of CD3+ cells was also significantly (p&lt;0.01) decreased in stage III and IV tumors (5.23% and 4.46%, respectively), comparing to control (11.66%), and stage I and II tumors (13.57% and 7.4%).
Our results indicate significant immunosuppression in patients with advanced tumors that can be related to high MDSCs level. High level of these cells may be also related with metastasis formation in patients with advanced tumors.
This work was supported by grant no IP2011 027171 from the Ministry of Sciences and Higher Education.
Citation Format: Joanna Mucha, Agata Homa, Kinga Majchrzak, Tomasz Motyl, Magdalena Król. The number of MDSC (Gr1+/CD11b+) and T lymphocytes in blood of canine patients during mammary and skin tumors development. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A56.
Abstract A74: The chemoattractant chemerin suppresses melanoma by recruiting natural killer cell antitumor defenses.
Authors: Pachynski Russell , Zabel Brain , Monnier Justin , Gentles Andrew , Swanson Christina , Kohrt Holbrook , Hadeiba Husein , Alizadeh Ash , Butcher Eugene 
Published: August 2014

Abstract
Infiltration of specialized immune cells regulates the growth and survival of neoplasia. Here, in a survey of public whole genome expression datasets we found that the gene for chemerin, a widely expressed endogenous chemoattractant protein, is down-regulated in melanoma as well as other human tumors. Moreover, high chemerin messenger RNA expression in tumors correlated with improved outcome in human melanoma. In experiments using the B16 transplantable mouse melanoma, tumor-expressed chemerin inhibited in vivo tumor growth without altering in vitro proliferation. Growth inhibition was associated with an altered profile of tumor-infiltrating cells with an increase in natural killer (NK) cells and a relative reduction in myeloid-derived suppressor cells and putative immune inhibitory plasmacytoid dendritic cells. Tumor inhibition required host expression of CMKLR1 (chemokine- like receptor 1), the chemoattractant receptor for chemerin, and was abrogated by NK cell depletion. Intratumoral injection of chemerin also inhibited tumor growth, suggesting the potential for therapeutic application. Preliminary data in other adenocarcinoma tumor types (eg breast) show similar results, supporting broad applicability of such an approach. These results show that chemerin, whether expressed by tumor cells or within the tumor environment, can recruit host immune defenses that inhibit tumorigenesis and suggest that down-regulation of chemerin may be an important mechanism of tumor immune evasion.
Citation Format: Russell Pachynski, Brain Zabel, Justin Monnier, Andrew Gentles, Christina Swanson, Holbrook Kohrt, Husein Hadeiba, Ash Alizadeh, Eugene Butcher. The chemoattractant chemerin suppresses melanoma by recruiting natural killer cell antitumor defenses. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A74.
Abstract A76: Comparative mRNA and microRNA expression profiling of canine mammary carcinoma cell lines and macrophages grown as a co-culture in vitro.
Authors: Król Magdalena , Pawlowski Karol , Majchrzak Kinga , Majewska Alicja , Motyl Tomasz 
Published: August 2014

Abstract
Solid tumors comprise of various cells, including cancer cells, resident stromal cells, migratory haemopoietic cells and other. These cells regulate tumor growth and metastasis. Macrophages constitute probably the most important element of all interactions within the tumor microenvironment. However, the molecular mechanism, that guides tumor environment, still remains unknown. Exploring the underlying molecular mechanisms that orchestrate these phenomena has been the aim of our study.
The co-cultures of five various canine mammary carcinoma cell lines and macrophages were established and maintained for 72 hrs. After that, having sorted the cells, an integrated analysis of genome-wide mRNA and microRNA expression profiles have been assessed.
The analysis showed that the up-regulated genes in the cancer cell lines grown as co-culture with macrophages are involved mainly in: macrophages activation, cell motion, mammary gland development, cell-cell adhesion, and angiogenesis. Basides, the presence of macrophages in the cancer environment induces acquisition of the macrophage antigens and phenotype in cancer cells.
The up-regulated genes in macrophages grown as co-cultre with cancer cells were involved mainly in cell-cell adhesion and cell-matrix adhesion.
We found that co-culture of cancer cells and macrophages regulates expression of several important miRNAs.
Taken together, this integrated comparative study generated a scheme of the molecular changes that occur during interactions between macrophage and cancer. Because as far as we realize this is the first analysis of changes in miRNA expression in cancer cells due to a presence of macrophages, our study can serve as a valuable source for future studies on a tumor microenvironment, and some of the highlighted genes, miRNAs, pathways or processes may be useful for diagnostic or therapeutic purposes.
This work was supported by grant no N N308012939 from the Ministry of Sciences and Higher Education.
Citation Format: Magdalena Król, Karol Pawlowski, Kinga Majchrzak, Alicja Majewska, Tomasz Motyl. Comparative mRNA and microRNA expression profiling of canine mammary carcinoma cell lines and macrophages grown as a co-culture in vitro. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A76.
Abstract A94: Imatinib modulates CD4+ T cells in gastrointestinal stromal tumor (GIST).
Authors: Balachandran Vinod P. , Cavnar Michael , Zeng Shan , Bamboat Zubin , Ocuin Lee , Obaid Hebroon , Sorenson Eric , Kim Teresa , Popow Rachel , DeMatteo Ronald P. 
Published: August 2014

Abstract
Introduction: Imatinib mesylate partially exerts its antitumor effects in GIST by inhibiting tumor production of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (Ido), thereby activating antitumor CD8+ T cells. The role of conventional CD4+ T cells (CD4+FoxP3-) in imatinib therapy is unknown. We examined the effects of imatinib on CD4+ T cells in GIST.
Methods: We injected imatinib or saline intraperitoneally for one week to KitV558-/+ mice that develop spontaneous GISTs. 1-methyl-D-tryptophan (D-1MT), an Ido inhibitor was given via oral gavage. We assessed treatment response by tumor weight and immune cells by flow cytometry. Regulatory T cells (Treg) were defined as CD4+FoxP3+. Matched blood and tumor specimens from GIST patients were freshly analyzed for immune composition. Tumors were classified as untreated, sensitive, or resistant to imatinib based on radiologic assessment just before the time of surgery.
Results: Imatinib increased CD4+ number, activation, and degranulation in the draining lymph node (DLN) but not the spleen of GIST mice (p&lt;0.05). In the tumor, imatinib increased CD4+ number, activation, proliferation, and the intratumoral CD4+/Treg ratio (p&lt;0.05). Conversely, Ido inhibition did not alter CD4+ number, activation, proliferation, or the CD4+/Treg ratio in the DLN or tumor. In untreated human GISTs (n=14), CD4+ T cells demonstrated greater activation and memory phenotype compared to autologous blood CD4+ T cells, but secreted Th2 cytokines on in vitro restimulation (p&lt;0.05). Imatinib treatment altered the intratumoral CD4+/Treg ratio, with a higher ratio in sensitive tumors (n=17) compared to resistant tumors (n=12; p&lt;0.05).
Conclusion: In mouse GIST, imatinib activates CD4+ T cells independently of Ido and increases the intratumoral CD4+/Treg ratio, a hallmark of immunologic outcome. Similarly, imatinib sensitive human GISTs have a higher CD4+/Treg ratio than resistant tumors. Hence, CD4+ T cells may contribute to the antitumor effects of imatinib in GIST. Combination immunotherapy with imatinib and CD4+ T cell modulating agents may be a promising therapy for GIST.
Citation Format: Vinod P. Balachandran, Michael Cavnar, Shan Zeng, Zubin Bamboat, Lee Ocuin, Hebroon Obaid, Eric Sorenson, Teresa Kim, Rachel Popow, Ronald P. DeMatteo. Imatinib modulates CD4+ T cells in gastrointestinal stromal tumor (GIST). [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A94.
Abstract B32: Preclinical testing of three immune adjuvants in vaccination therapy for invasive canine meningioma.
Authors: Andersen Brian M. , Pluhar G Elizabeth , Seiler Charles E. , Xiong Zhengming , Goulart Michelle R. , O'Sullivan Matthew Gerry , Hunt Matthew A. , Schiaffo Charles E. , Ferguson David M. , Ohlfest John R. 
Published: August 2014

Abstract
Malignant and atypical meningiomas are resistant to standard therapies, but therapeutic vaccines have not been tested preclinically or clinically. Pet dogs with naturally occurring meningioma are an underutilized model for aggressive human meningioma and an outstanding opportunity for assessing experimental therapeutic approaches. We treated 11 meningioma-bearing dogs with surgery and vaccine immunotherapy consisting of autologous tumor cell lysate combined with CpG or imiquimod. Interferon gamma-elaborating T cells were detected in the peripheral blood of two of cases, but vaccine-induced tumor-reactive antibody responses were found in the sera of all dogs. Systemic antibody responses were polyclonal, recognizing intracellular and cell surface antigens, and heat shock protein 60 was identified as one common antigen. Tumor-reactive antibodies bound allogeneic canine and human meningiomas, demonstrating common antigens across breed and species. Histological analysis revealed robust infiltration of antibody-secreting plasma cells into the brain around the tumor in treated compared to pre-treatment samples. Tumor-reactive antibodies were capable of inducing antibody dependent cell-mediated cytotoxicity to autologous and allogeneic tumor cells. Moreover, median survival for lysate/CpG and lysate/imiquimod vaccination was 646 days versus 222 days in historic surgery controls (p&lt;0.05). Compared to CpG, a novel imidazoquinoline with TLR7/8 and inflammasome activity, compound 528, was equally potent at activating canine PBMCs. A prospective randomized two-arm trial was recently launched, using lysate—compound 528 vaccines, versus surgery controls. Mean follow-up is 139 days at the time of writing, and recruitment is ongoing. These data demonstrate the feasibility and immunologic efficacy of vaccine immunotherapy for treating a large animal model of human meningioma and warrant further development towards human trials.
Citation Format: Brian M. Andersen, G Elizabeth Pluhar, Charles E. Seiler, Zhengming Xiong, Michelle R. Goulart, Matthew Gerry O'Sullivan, Matthew A. Hunt, Charles E. Schiaffo, David M. Ferguson, John R. Ohlfest. Preclinical testing of three immune adjuvants in vaccination therapy for invasive canine meningioma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B32.
Abstract B44: Enabling in vivo visualization of cellular therapies in the clinic: Maturation of αDC1 data sets.
Authors: Helfer Brooke M. , Balducci Anthony , Urban Julie , Butterfield Lisa , Ahrens Eric , Kalinski Pawel , Wesa Amy 
Published: August 2014

Abstract
Cellular therapies are increasingly being used in the clinic to modify a patient's immune function. Human dendritic cells (DC) have great clinical promise as an immunotherapeutic intervention against cancer, but questions concerning the dispersion and persistence of these cells, as well as correlations to therapeutic potency remain. Here we utilize a perfluoropolyether (PFPE) magnetic resonance imaging (MRI) tracer agent that aims to address these questions in the assessment of α-type-1-polarized dendritic cells (αDC1). αDC1 cells, producing high levels of interleukin-12p70 with putative strong lymph node homing capabilities, have been evaluated in support of an IND incorporating post-transfer MR imaging of the therapeutic cells. Important therapeutic functions, such as cytokine production, cellular phenotype, and antigen processing are maintained. Transitioning the protocol from the laboratory into clinical production, taking into account GMP procedural changes, resulted in both maintained cellular properties and detectable signal by 3T MRI.
In vivo results demonstrate the capability of MRI to detect and quantify labeled cells with a high degree of specificity. With nominal exogenous fluorine naturally present in tissue, labeled cells appear with little background. Pairing this signal with conventional proton MRI from the same imaging session, cells are able to be traced to their precise anatomical location. The MRI tracking capabilities, safety profiles, and use of 19F labeling in preclinical data sets demonstrate the ability of 19F to be used in clinical applications to strengthen the understanding of cellular therapeutics.
Citation Format: Brooke M. Helfer, Anthony Balducci, Julie Urban, Lisa Butterfield, Eric Ahrens, Pawel Kalinski, Amy Wesa. Enabling in vivo visualization of cellular therapies in the clinic: Maturation of αDC1 data sets. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B44.
Abstract B58: CD40 combined toll-like receptor 3 ligation restore morphine-induced reducing dendritic cells-mediating immunity and antitumor effect.
Authors: Chang Ming-Cheng , Chen Yu-Li , Sun Wei-Zen , Cheng Wen-Fang 
Published: August 2014

Abstract
Morphine has been regarded as a kind of medications with great effective for the management of postoperative pain in surgery and cancer pain with compromising host immunity. However, the mechanisms of how morphine influences the host immunity are still unclear. Our previous study has revealed that morphine could promote effector T cell apoptosis and suppress anti-tumor effect enhanced by antigen-specific DNA vaccine. In current study, we evaluated how morphine interrupted host immunity especially on dendritic cells (DCs) and the possible mechanisms. Morphine could delay the differentiation and maturation of the bone marrow monocyte (BMM)-derived DCs. Furthermore, morphine could inhibit the secretion of IL-6 and TNF-α; but stimulate the excretion of IL-10 from BMM-derived DCs. Besides, morphine could suppress the maturation processes of BMM-DC via the activation of MAPK and down-regulation of P38. When mice administrated with an adjuvant mixture containing the TLR3 ligand-poly (I:C) and agonistic anti-CD40 antibodies, a significant increase DCs property, antigen presenting activity and MAPK/ERK/p38 protection effects were observed. Finally, the TLR3 ligand-poly(I:C) and anti-CD40 Ab vaccinated mice treated with morphine could maintain the anti-tumor effects. Our findings reveal that morphine treatment suppressed DCs maturation and TLR3 ligand-poly(I:C) with anti-CD40 Ab administration may serve as a useful approach to treat the profound immunosuppressive function and prevent tumorigenesis after long-term morphine treatment.
Citation Format: Ming-Cheng Chang, Yu-Li Chen, Wei-Zen Sun, Wen-Fang Cheng. CD40 combined toll-like receptor 3 ligation restore morphine-induced reducing dendritic cells-mediating immunity and antitumor effect. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B58.