bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A17: Cancer immunotherapy using naked DNA vaccine targeting p53.
Authors: Soong Rueyshyang , Hung Chien-Fu , Wu T.-C. 
Published: August 2014

Abstract
Background: The pivotal role of p53 as a tumor suppressor protein is illustrated by the fact that this protein is found mutated in more than 50% of human cancers. In most cases, mutations in p53 greatly increase the otherwise short half-life of this protein in normal tissue and cause it to accumulate in the cytoplasm of tumors. The overexpression of mutated p53 in tumor cells makes p53 a potentially desirable target for the development of cancer immunotherapy. However, p53 protein represents an endogenous tumor-associated antigen (TAA), and immunization against self-antigen is challenging because antigen-specific immune response likely only generate low affinity antigen-specific CD8+ T cells. This represents a bottleneck of tumor immunotherapy when targeting endogenous antigens expressed by tumors.
Purpose: The objective of the current study is to develop a safe cancer immunotherapy using a naked DNA vaccine employing xenogenic p53 gene to break immune tolerance resulting in a potent therapeutic antitumor effect against tumors expressing mutated p53. Our study assessed the therapeutic antitumor effect after immunization with DNA encoding human p53 (hp53) or mouse p53 (mp53).
Results: C57BL/6 mice immunized with xenogenic full length of hp53 DNA plasmid intramuscularly followed by electroporation were capable of protecting against challenge with murine colon cancer MC38. In contrast, mice immunized with mp53 DNA were incapable of protecting mice against challenge with MC38 tumors. In a therapeutic model, established MC38 tumors were also well controlled by treatment with hp53DNA therapy in tumor bearing mice compared to mp53 DNA. Mice vaccinated with hp53 DNA plasmid also exhibited an increase in mp53-specific CD8+ T cell precursors compared to vaccination with mp53 DNA. In antibody depletion experiments, we also demonstrated that CD8+ T cells play crucial roles in the antitumor effects.
Conclusion: This study showed intramuscular vaccination with xenogenic hp53 DNA vaccine followed by electroporation is capable of inducing potent antitumor effects against mutated p53 expressing tumors through CD8+ T cells.
Citation Format: Rueyshyang Soong, Chien-Fu Hung, T.-C. Wu. Cancer immunotherapy using naked DNA vaccine targeting p53. [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 A17.
Abstract A29: An Ad5 [E1-, E2b-] platform carrying the TAA CEA(6D) induces CEA directed CMI responses in patients with advanced CEA-expressing colorectal cancer in a phase I/II clinical trial..
Authors: Morse Michael A. , Gabitzsch Elizabeth S. , Xu Younong , Rajesh Dua , Nguyen Susan , Balcaitis Stephanie , Balint Joseph P. , Jones Frank 
Published: August 2014

Abstract
First-generation, E1-deleted adenovirus (Ad)-based vectors, although promising platforms for use as cancer vaccines, are limited by the naturally occuring or induced Ad-specific neutralizing antibodies. We hypothesized that Ad5-based vectors with deletions of the E1 and the E2b regions (the latter encoding the DNA polymerase and the preterminal protein) would, by virtue of diminished late phase viral protein expression, avoid immunological clearance and induce more potent immune responses against the encoded tumor antigen transgene in Ad-immune hosts. In this translational study, we demonstrated that delivery of increasing doses of the Ad5 [E1-, E2b-]-CEA(6D) in mice resulted in CEA-specific cell-mediated immune (CMI) responses. In the follow-up human phase I/II study, escalating doses of the vaccine induced higher CEA-specific CMI responses despite the presence of pre-existing Ad5 immunity in a majority (76%) of patients. Importantly, there was minimal toxicity, and overall patient survival (54.1% at 12 months) was similar regardless of pre-existing Ad5 neutralizing antibody titers. The results demonstrate that the novel Ad5 [E1-, E2b-] gene delivery platform can both break tolerance and generate significant CMI responses to the TAA CEA in the setting of both naturally acquired Ad5-specific immunity and/or immunization-induced Ad5 immunity.
Citation Format: Michael A. Morse, Elizabeth S. Gabitzsch, Younong Xu, Dua Rajesh, Susan Nguyen, Stephanie Balcaitis, Joseph P. Balint, Jr., Frank Jones. An Ad5 [E1-, E2b-] platform carrying the TAA CEA(6D) induces CEA directed CMI responses in patients with advanced CEA-expressing colorectal cancer in a phase I/II clinical trial.. [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 A29.
Abstract A55: Inhibition of the heat shock protein receptor CD91 abrogates concomitant antitumor immunity.
Authors: Zhou Yu Jerry , Binder Robert J. 
Published: August 2014

Abstract
Most tumors are capable of generating immune response in the bearing host, a phenomenon described as concomitant immunity. Since tumors lack the typical (foreign) PAMPs that provide signal 2 for T cell priming, the mechanism of how concomitant immunity is established remains a mystery. We provide evidence here that, heat shock proteins (HSPs), when released into the tumor microenvironment, is the immunogen necessary for priming concomitant tumor specific immunity. These responses require CD91- the endocytic and signaling receptor for the immunogenic HSPs. In our study, we generated cd11c-specific CD91 knockout mice and showed that tumors grew faster in those knockout mice, compared to CD91+/+ mice. In addition, we abrogated the interaction of tumor-derived HSP with CD91 in vivo by over-expression of Receptor Associated Protein (RAP), an endogenous inhibitor of CD91. The data showed that: first, tumors expressing RAP grew with significantly faster kinetics than the non-RAP expressing counterparts in wild type mice, although this difference was non-existent in immunocompromised mice and the inherent proliferative rates of tumors with or without RAP were identical; second, RAP-expressing tumors, when used as an immunogen in tumor prophylaxis, were significantly less efficient in priming immune responses; third, we examined the competition for CD91 between RAP and tumor-derived HSP in vivo. In the presence of RAP, less amount of tumor-derived EGFP-labeled HSPs were taken up by APCs in draining lymph nodes. In summary, our study demonstrates that the HSP-CD91 pathway is critical for establishment of concomitant immunity. Considering that elevated RAP levels have been reported in colon cancer patients, we propose a novel mechanism of immune evasion for tumors expressing competing ligands for immune receptors such as CD91.
Citation Format: Yu Jerry Zhou, Robert J. Binder. Inhibition of the heat shock protein receptor CD91 abrogates concomitant antitumor immunity. [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 A55.
Abstract A7: TARP-TCR-engineered T cells specifically kill HLA-A2 positive prostate and breast cancer cells.
Authors: Hillerdal Victoria , Nilsson Berith , Carlsson Bjorn , Eriksson Fredrik , Essand Magnus 
Published: August 2014

Abstract
In order to produce genetically engineered T cells directed against prostate and breast cancer cells we have cloned the T cell receptor recognizing the human leukocyte antigen (HLA)-A2-restricted TARP4-13 epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. Peripheral blood T cells transduced with a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptide-specific stimuli. They exerted peptide-specific interferon-γ production and cytotoxic activity. Importantly, HLA-A2+ prostate and breast cancer cells expressing TARP were also killed, demonstrating that the TARP4-13 epitope is a physiologically relevant target for T cell therapy of prostate and breast cancer. In conclusion, we present the cloning of a TCR directed against a physiologically relevant HLA-A2 epitope of TARP. To our knowledge this is the first report on engineering of T cells with a TCR directed against an antigen specifically expressed by prostate cells.
Citation Format: Victoria Hillerdal, Berith Nilsson, Bjorn Carlsson, Fredrik Eriksson, Magnus Essand.TARP-TCR-engineered T cells specifically kill HLA-A2 positive prostate and breast cancer cells. [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 A7.
Abstract A70: Interactions between dendritic cells and T lymphocytes in a novel 3-D environment.
Authors: Steponavicius-Cruz Karen , Freitas Vanessa Morais , Barbuto José Alexandre Marzagão 
Published: August 2014

Abstract
Introduction: Dendritic cells (DCs) are the major antigen-presenting cells and, in situations of change in homeostasis, are able to initiate immune responses through the activation of T lymphocytes. Their immunomodulatory functions and generation in vitro are of great potential for immunotherapy of cancer. Among the many strategies under investigation, one, which our group has been using, is based on the fusion of DCs and tumor cells for therapeutic vaccination. To better understand the interactions between these fused DC-tumor cell hybrids and the different T cell populations, we are developing a three-dimensional (3D) culture system, whose first results are presented here.
Methods and Results: Monocytes of healthy donors were purified from PBMCs by magnetic beads selection and induced to differentiate into DCs by treatment with GM-CSF and IL-4. Maturation of monocyte-derived DCs (mMo-DCs) was initiated by addition of TNF-alpha 48 hours or 2.5 hours before analysis. Immature DCs were generated for 7 days in the absence of a maturation stimulus. Allogeneic T lymphocytes were purified from PBMCs by magnetic beads selection and were co-cultured for 17 hours in the 3D Biotek scaffold, at 37 °C. These scaffolds are made from polystyrene and have a thickness of 600 μm, fibers of 150 μm and pores of 200 μm. In this system, mMO-DCs TNF-activated for 2.5 h did not interact with allogeneic T lymphocytes, while those activated for 48 hours did. The average time of interaction between mMo-DCs and T lymphocytes was 4 hours, and the average speed of the T lymphocytes in the scaffold containing 48h-activated mMO-DCs was of 0.94 µm/min. Immature DCs interact with allogeneic T lymphocytes and the average time of interaction was 57 minutes. The average speed of the T lymphocytes in the scaffold containing immature DCs was of 0.93 µm/min.
Conclusions: These data indicate that this 3D Biotek scaffold enables interactions between mMO-DCs and lymphocytes and may be useful for the characterization of these interactions, the cellular subtypes and patterns of response induced. Financial Support: FAPESP (2010/18139-7; 2009/54599-5; CNPq).
Citation Format: Karen Steponavicius-Cruz, Vanessa Morais Freitas, José Alexandre Marzagão Barbuto. Interactions between dendritic cells and T lymphocytes in a novel 3-D environment. [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 A70.
Abstract B19: Tumor-specific structural rearrangements as potential targets for anticancer vaccines.
Authors: Martin Spencer David , Wick Darin A. , Webb John R. , Holt Robert A. , Nelson Brad H. 
Published: August 2014

Abstract
A hallmark of cancer is the accumulation of mutations that allow cells to proliferate uncontrollably. Every tumor has a unique set of somatic mutations, which can be identified with next generation sequencing. In theory, CD8+ T cells can recognize mutated proteins present in human cancers if the mutations are presented as peptides bound to MHC class I molecules. We hypothesize that personalized, tumor-specific peptide vaccines will activate CD8+ T cells and induce tumor regression. To test this concept, we subjected four mouse mammary tumors to RNA sequencing using the Illumina sequencing platform. We identified 14 somatic point mutations and one fusion transcript unique to these tumors. In addition, we have optimized a vaccination strategy involving long peptides and the adjuvant poly (I:C) that results in massive proliferation of antigen-specific CD8+ T cells. When we used this optimized vaccination protocol to target tumor specific mutations, a strong T cell response was elicited towards the fusion protein, but only weak responses or no responses were elicited towards the point mutations. Currently, we are vaccinating mice with immunogenic mutated-peptides, and assessing whether the T cell response elicited by the vaccines causes regression or rejection of established tumors that harbor the same mutations. As the cost of sequencing the human genome continues to decrease, personalized vaccines that target tumor-specific mutations may become a treatment strategy that is clinically feasible.
Citation Format: Spencer David Martin, Darin A. Wick, John R. Webb, Robert A. Holt, Brad H. Nelson. Tumor-specific structural rearrangements as potential targets for anticancer vaccines. [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 B19.
Abstract B29: Improving the identification of beneficial mimotopes using a representative tumor-specific T cell receptor.
Authors: Slansky Jill E. , Buhrman Jonathan D. 
Published: August 2014

Abstract
Vaccination with peptide mimotopes is a promising strategy to improve antitumor immunity. Mimotopes function by eliciting increased numbers of T cells that cross-react with the native tumor antigen. Using a high affinity tumor-specific T cell clone (CT), we have identified a panel of mimotopes for the dominant antigen (AH1) of a mouse colon tumor cell-line (CT26) that elicits a range of tumor protection when used in vaccines. Ex vivo evaluation of the TCRs of T cells initiated by mimotopes that protect against tumor challenge revealed increased representation of a Vβ8.3/Jβ2.6 motif: a small hydrophobic amino acid, followed by a large polar residue, and the tyrosine of the Jβ2.6. Clonotypes with this motif were also identified within the AH1-specific T cell repertoire of naturally responding TIL and following vaccination with the AH1 antigen. This motif was not found in the original CT clone. One particular clone with the motif made up nearly 8.5% of all Vβ8.3 sequences identified following immunization with mimotopes. Thus, we tested the hypothesis that this ‘representative’ TCR improves the frequency of discovery of efficacious mimotopes for cancer immunotherapy relative to the high affinity CT clone in the CT26 model. We have demonstrated that this is the case by screening genetically encoded peptide libraries. These results have important implications when considering the optimal T cells responding to tumor antigens and the improved identification of mimotopes for cancer immunotherapy.
Citation Format: Jill E. Slansky, Jonathan D. Buhrman. Improving the identification of beneficial mimotopes using a representative tumor-specific T cell receptor. [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 B29.
Abstract B47: Neural cells labeling with intracerebral ferumoxytol iron oxide nanoparticles in a rat model.
Authors: Wu Yingjen Jeffrey , Muldoon Leslie L. , Neuwelt Edward A. 
Published: August 2014

Abstract
Purpose: To investigate uptake of ferumoxytol iron oxide nanoparticles into rat neural cells for a clinically applicable magnetic resonance (MR) imaging technique.
Materials and Methods: Long Evan rats were injected with intracerebral ferumoxytol (360 μg) iron oxide nanoparticles into the right hemisphere. A needle track in the left hemisphere was used as a sham control. Animals underwent T2-weighted fast spin-echo MRI sequences at 12T 48 h after nanoparticle inoculation. Immediately after MRI, single brain cell suspensions were produced from the right and left hemispheres, and neurospheres were stained for iron using Prussian blue histochemstry.
Results: The ferumoxytol-injected right hemisphere showed decreased T2 signal compared to the sham injected left hemisphere. Positive iron staining was found in neural cells from the right cerebral hemisphere, although &lt;5% of total cell number, while no positive iron staining cells were found in the left hemisphere. The decreasing T2 signal does not correlate the percentage of neural cells labeled with ferumoxytol iron oxide nanoparticles, indicating most of the nanoparticles were not cell-associated. The phenotypes of ferumoxytol-labeled neural cells will be characterized by immunohistochemistry for neural markers. No neural cell in vitro labeling was detected using ferumoxytol in combination with protamine sulfate and heparin.
Conclusion: Iron oxide loading of neural cells in the brain parenchyma can be achieved with the clinically approved agent ferumoxytol. Iron labeling may be utilized to monitor neuro-inflammation and brain tumors after chemotherapy for non-invasive MRI.
Citation Format: Yingjen Jeffrey Wu, Leslie L. Muldoon, Edward A. Neuwelt. Neural cells labeling with intracerebral ferumoxytol iron oxide nanoparticles in a rat model. [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 B47.
Abstract B48: Resensitization to CDDP or trail-mediated apoptosis in ovarian cancer cells by Obatoclax.
Authors: Martinez-Paniagua Melisa A. , Romero-Gonzalez Luis A. , Anguiano-Hernandez Yu-Mei , Gonzalez-Torres Carolina , Vega Mario I. 
Published: August 2014

Abstract
Ovarian cancer is the fifth cause of death in women, annually 13,850 deaths are reported in United States. Chemo is the conventional therapy after surgery but the initial response is between 60 to 80%, however, some patients that initially respond well to the therapy suffer recurrent disease or become resistant to the treatment. As a consequence, the overall 5 year survival is only 30%. There is a necessity to identify novel therapies for ovarian cancer or to discover drugs witch re sensitize tumor cells to existence therapy. It has been suggested that the resistance of the tumor cells is because of the increased expression of antiapoptotic proteins especially from the Bcl2 family (Bcl-2, Bcl-XL, Mcl-1). Obatoclax is a small molecule that mimics the BH3 domain of the BH3 only family members, inhibiting the effect of antiapoptotic Bcl-2 members. The objective of this study was to assess the susceptibility of ovarian cancer cell lines to chemo or immune therapy mediated apoptosis by obatoclax and also to elucidate the mechanism. Some ovarian cancer cell lines were treated with different concentrations of Obatoclax, CDDP or TRAIL alone or in combinational treatment to assess the reduction of viability measured by the XTT kit (Roche). Basal and cell treated total protein expressions were assessed by western. Induction of apoptosis was measured by TUNEL. As a single agent, Obatoclax or CDDP inhibited the growth of ovarian cancer cell lines in a dose response manner, TRAIL was no having an evident response showing a plateau with the concentration used. The combinational treatment after selecting the IC50 and IC20 response showed an increased inhibition of the viability. The induction of apoptosis was mediated by a caspase dependent manner. Our data suggest that obatoclax in combination with CDDP or TRAIL can re sensitize resistance cell lines to apoptosis and also it can be an optional treatment of patients with ovarian cancer.
Citation Format: Melisa A. Martinez-Paniagua, Luis A. Romero-Gonzalez, Yu-Mei Anguiano-Hernandez, Carolina Gonzalez-Torres, Mario I. Vega. Resensitization to CDDP or trail-mediated apoptosis in ovarian cancer cells by Obatoclax. [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 B48.
Abstract B52: A novel quantitative proteomics approach to identify proteins that elicit antibody responses in vaccinated pancreatic cancer patients.
Authors: Jhaveri Darshil T. , Kim Min-Sik , Huang Lanqing , Sharma Rajni , Anders Robert A. , Pandey Akhilesh , Jaffee Elizabeth M. 
Published: August 2014

Abstract
Pancreatic cancer is the fourth leading cause of cancer deaths in the US. Less than 4% of patients have an overall survival of more than 5 years. Our lab has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting pancreatic cancer vaccine that has recently completed phase II clinical trials. The application of proteomic approaches has gained ground in the identification of new cancer biomarkers, which are beneficial for both early detection and determination of new targets for development of biologically relevant therapies. We have developed a novel Serum Antibodies based SILAC-Immunoprecipitation (SASI) approach. The SASI approach utilizes immunoprecipitation by serum antibodies, which is coupled to the quantitative stable isotope labeling by amino acids in cell culture (SILAC) to identify proteins that elicit an increased antibody response post-vaccination. Using mass spectrometric analysis, the SASI approach comprehensively identified &gt;40 proteins that elicited at least a 2-fold increase in antibody response post-vaccination, from each of the three patients' sera used. The list of identified proteins includes membrane proteins such as MHC class I complex, transferrin receptor (TFRC) and CD9, secreted proteins such as mesencephalic astrocyte-derived neurotrophic factor (MANF), as well as several cytoplasmic proteins such as regulatory subunit 12A of protein phosphatase 1 (PPP1R12A), galectin 3 and regulatory subunit 8 of the 26S proteasome (PSMC5). Most significantly, the antibody responses detected against these proteins in patients with &gt;3 years disease-free survival suggests an anti-tumor potential of targeting these proteins. We further analyzed PSMC5, TFRC and PPP1R12A for tissue expression in normal, pre-malignant and pancreatic tumor specimens and found these proteins to increase in expression with tumor development. In addition, these proteins were shown to be pancreatic cancer associated antigens that are recognized by post-vaccination antibodies in the sera of patients that received the vaccine and have demonstrated a favorable disease free survival. Overall, our data demonstrates that the novel SASI approach can enable identification of candidate proteins as possible new biomarkers for screening, and as new targets for therapeutic intervention.
Citation Format: Darshil T. Jhaveri, Min-Sik Kim, Lanqing Huang, Rajni Sharma, Robert A. Anders, Akhilesh Pandey, Elizabeth M. Jaffee. A novel quantitative proteomics approach to identify proteins that elicit antibody responses in vaccinated pancreatic cancer patients. [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 B52.