bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2882: p53MVA therapy in patients with refractory gastrointestinal malignancies primes robust CD8+ T cell responses
Authors: Hardwick Nicola , Carroll Mary , Kaltcheva Teodora , Qian Dajun , Espenschied Jonathan , Leong Lucille , Chu Peiguo , Kim Joseph , Chao Joseph , Fakih Marwan , Ellenhorn Joshua , Diamond Don , Chung Vincent 
Published: May 2015

Abstract
PURPOSE: To conduct a Phase I safety trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in patients with refractory gastrointestinal malignancies.
EXPERIMENTAL DESIGN: Three patients were vaccinated with 108 pfu p53MVA followed by nine patients at 5.6 x 108 pfu. Toxicity was classified using the NCI Common Toxicity Criteria and clinical responses were assessed by CT scan. Peripheral blood samples were collected pre vaccine and post vaccination for immunophenotyping and assessment of p53MVA induced immune response.
RESULTS: p53MVA immunization was well tolerated at both doses, with no adverse events above grade 2. Induction of strong T cell and antibody responses to the MVA backbone were apparent. CD4+ and CD8+ T cells showing enhanced recognition of a p53 overlapping peptide library were detectable after the first immunization, particularly in the CD8+ T cell compartment (p=0.03). However in most patients this did not expand further with the second and third immunization. Some patients exhibited a decline in myeloid-derived suppressor cells post vaccine, but this was not statistically significant. The frequency of PD-1+ T cells detectable in patients PBMC was significantly higher than healthy controls. Furthermore, the frequency of PD-1+ CD8+ T cells showed an inverse correlation with the peak CD8+ T cell response to p53 (p=0.02).
CONCLUSION: p53MVA was well tolerated and induced robust CD8+ T cell responses. Combination of p53MVA with immune checkpoint inhibition could improve sustained immune responses and lead to clinical benefit.
Citation Format: Nicola Hardwick, Mary Carroll, Teodora Kaltcheva, Dajun Qian, Jonathan Espenschied, Lucille Leong, Peiguo Chu, Joseph Kim, Joseph Chao, Marwan Fakih, Joshua Ellenhorn, Don Diamond, Vincent Chung. p53MVA therapy in patients with refractory gastrointestinal malignancies primes robust CD8+ T cell responses. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2882. doi:10.1158/1538-7445.AM2014-2882
Abstract 2888: Dendritic cell-targeted lentiviral vector vaccines overcome tolerance to generate a protective T-cell immune response to breast cancer antigens ERBB2 and α-lactalbumin
Authors: Bryson Paul D. , Han Xiaolu , Truong Norman , Wang Pin 
Published: May 2015

Abstract
Breast cancer immunotherapy is a potent treatment option, with antibody therapies such as trastuzumab increasing 2-year survival rates by 50%. In contrast, active immunotherapy through therapeutic vaccination has yet to be proven clinically effective for breast cancer. One potential means of improving vaccine therapy is by delivering breast cancer antigens to dendritic cells (DCs) for enhanced antigen presentation. To achieve this in vivo, we have pseudotyped lentiviral vector vaccines with a modified Sindbis Virus glycoprotein that targets the C-type lectin DC-SIGN, which is expressed on DCs. We hypothesized that utilizing these DC-targeting lentiviral vectors as a breast cancer vaccine could lead to an improved immune response against self antigens found in breast cancer tumors. Such an improved immune response may help to prevent or slow tumor growth in breast cancer models. To test these hypotheses, we have constructed lentiviral vectors encoding each of the breast cancer antigens, human Her2 (ERBB2) and mouse alpha-lactalbumin (Lalba). Single injections were able to amplify antigen-specific CD8 T cells to 1.6% of total CD8 T cells in BALB/cJ mice and 0.7% in transgenic ERBB2 mice. This compares favorably with recently published vector vaccines, which have elicited 0.9% and &lt;0.1% antigen-specific CD8 T cells under similar conditions. In addition, DC-targeted immunization of these mice completely inhibited tumor growth in a foreign antigen environment (ERBB2 + wt BALB/cJ), while it significantly reduced the rate of tumor growth in a self-antigen environment (Lalba + BALB/cJ or ERBB2 + FVB/Tg.MMTV.f.huHER2 #5). Our data show that these vectors alone can provide an effective therapy. Future studies may be able to improve these responses by combining DC-targeted immunization with established methods of reducing cancer immunosuppression. Thus, lentivector vaccines may be an excellent component to future clinical vaccine trials, either by themselves or in combination with other chemo- and immunotherapies.
Citation Format: Paul D. Bryson, Xiaolu Han, Norman Truong, Pin Wang. Dendritic cell-targeted lentiviral vector vaccines overcome tolerance to generate a protective T-cell immune response to breast cancer antigens ERBB2 and α-lactalbumin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2888. doi:10.1158/1538-7445.AM2014-2888
Abstract 2891: Bench-to-bedside development of a novel idiotype vaccine against lymphoma
Authors: Qin Hong , Cha Soungchul , Rao Sheetal S. , Kim Kunhwa , Gwak Dongho , Kim Sung-doo , Parshottam Sapna R. , Thomas Sheeba K. , Kwak Larry W. 
Published: May 2015

Abstract
Available therapies for lymphoplasmacytic lymphoma (LPL) provide no survival advantage if started before symptoms of end organ damage develop. Current recommendations are to follow a program of observation while patients are in the asymptomatic phase of disease. In this clinical study we will use idiotypic determinants of B-cell lymphoma surface immunoglobulins as tumor-specific antigens (idiotype) to develop a patient-specific vaccine against LPL. By activating the host immune system through vaccination to eradicate tumor cells, we postulate that disease control of asymptomatic phase lymphoplasmacytic lymphoma can be maintained. This novel 2nd generation idiotype vaccine was initially developed by genetic fusion of idiotype antigen in single-chain format with a pro-inflammatory chemokine. The central hypothesis is that antitumor immunity can be triggered by targeting antigen delivery to antigen-presenting cells in vivo by chemokine receptor-mediated binding, uptake and processing of idiotype antigens for more efficient presentation to T cells. A large body of preclinical data demonstrated that the immunogenecity of the idiotype antigen was considerably enhanced by such a genetic modification by a mechanism of facilitating antigen presentation. As a consequence, vaccine-induced prophylactic and therapeutic antitumor effects were significantly potentiated. To translate our vaccine therapy from bench to bedside, we established a CLP laboratory for vaccine preparation. Furthermore, we developed reliable technology to differentiate lymphoma idiotype antigens from idiotypic cell-surface immunoglobulins on normal B cells. Using this technology, we successfully cloned the cDNA encoding variable regions of heavy and light chains of LPL idiotype, and generated patient-specific plasmid constructs containing LPL idiotype single chain in fusion with macrophage inflammatory protein 3 alpha (MIP3a). All three engineering rounds of down-stream GMP amplification of clinical-grade plasmid DNA have been accomplished, which eventually paves the way for us to take a lab-grown agent to a first-in-human clinical trial.
Citation Format: Hong Qin, Soungchul Cha, Sheetal S. Rao, Kunhwa Kim, Dongho Gwak, Sung-doo Kim, Sapna R. Parshottam, Sheeba K. Thomas, Larry W. Kwak. Bench-to-bedside development of a novel idiotype vaccine against lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2891. doi:10.1158/1538-7445.AM2014-2891
Abstract 2892: Vaccination with a therapeutic cancer vaccine containing prostate specific antigen and the biological adjuvants IL-2 and GM-CSF results in reduced serum PSA in prostate cancer patients
Authors: Head Jonathan F. , Elliott Robert L. 
Published: May 2015

Abstract
In 1997 we initiated a phase I/II clinical trial of a therapeutic prostate cancer vaccine. We have enrolled 12 biopsy confirmed prostate cancer patients in this study and 11 finished the initial course of 6 intradermal vaccinations containing prostate specific antigen (50 μg) and biological adjuvants (IL-2, 20,000 units, and GM-CSF, 16.7 μg) at 0, 1, 2, 6, 10 and 14 weeks. During this study the prostate cancer patients received no other concurrent therapy (surgery, hormone, radiation, radioactive seeds, chemotherapy). One of the 12 patient's PSA rose from 7.6 to 13.7 after the fourth vaccination and he (patient #8) withdrew from the study to seek other therapy. In the remaining 11 prostate cancer patients serum PSA concentrations were determined before initiating vaccination and 3-4 weeks after the 6th vaccination. There was a decrease in the PSA levels in 8 of 12 of the prostate cancer patients after 6 vaccinations. One of the patients (patient #3), whose PSA had dropped from 6.8 to 6.4 and had previously received radiotherapy (the only patient previously treated), elected to withdraw from the study and underwent radical prostatectomy. Nine of the original 12 patients have received monthly 3 intradermal IL-2 injections (11 million units) alternated with 3 further vaccinations for the 6 months following the initial vaccinations, and 8 patients have been followed from 18 to 92 months. The mean PSA values for the 8 patients still being followed without additional therapy were 5.8 initially, decreasing to 4.1 after 6 vaccines, 3.7 after 12 vaccines and is 4.7 after a mean follow-up of 49 months (median follow-up of 45.5 months). These promising results have led to the creation of the U.S. Navy Cancer Vaccine Program with a Phase I clinical trial at the Veterans Administration Medical Center San Diego/UCSD Medical School.
Citation Format: Jonathan F. Head, Robert L. Elliott. Vaccination with a therapeutic cancer vaccine containing prostate specific antigen and the biological adjuvants IL-2 and GM-CSF results in reduced serum PSA in prostate cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2892. doi:10.1158/1538-7445.AM2014-2892
Abstract 2898: HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma
Authors: Aref Ahmed M. , Hoa Neil T. , Ge Lisheng , Agrawal Anshu , Dacosta-Iyer Maria , Lambrecht Nils , Ouyang Yi , Cornforth Andrew N. , Jadus Martin R. 
Published: May 2015

Abstract
Immunotherapy for human hepatocellular cancer (HCC) is slowly making progress towards treating these fatal cancers. The identification of new antigens can improve this approach. We describe a possible new antigen, Hepatocellular Carcinoma-associated Antigen-519/ Targeting Protein for Xklp-2 [HCA519/Tpx2], for HCC that might be beneficial for T cell specific HCC immunotherapy. HCC was studied for the expression for 15 tumor-associated antigens considered useful for immunotherapy within three HCC cell lines (HepG2, Hep3B and PLC/PRF/5), lymphocytes, non-cancerous livers and clinical HCC. The expression of Tumor Antigenic Precursor Proteins (TAPPs) mRNA was first screened by quantitative real time PCR. Four antigens (alpha fetoprotein, aspartyl/asparaginyl β-hydroxylase, glypican-3 and HCA519/Tpx2) proved to be the best expressed TAPPs within the HCC specimens by molecular analyses. HCA519/Tpx2 was detected by intracellular cell flow cytometry within HCC cell lines by using a specific antibody towards this TAPP. This antibody also detected the protein within primary HCCs. We synthesized two HCA519/Tpx2 peptides (HCA519464-472 and HCA519351-359) which can bind to HLA-A*0201. Dendritic cells pulsed with these peptides stimulated cytolytic T lymphocytes (CTLs). These killer T cells lysed HLA-A*0201+ T2 cells exogenously loaded with the correct specific peptide. The CTLs killed HepG2 (HLA-A2+ and HCA519+), but not the Hep3B and PLC/PRF/5 cell lines, which are HCA519+ but HLA-A2-negative. In silico analysis reveals that HCA519/Tpx2 has the inherent ability to bind to a very wide variety of HLA antigens. HCA519/Tpx2 is a viable immunotarget that should be further investigated.
Citation Format: Ahmed M. Aref, Neil T. Hoa, Lisheng Ge, Anshu Agrawal, Maria Dacosta-Iyer, Nils Lambrecht, Yi Ouyang, Andrew N. Cornforth, Martin R. Jadus. HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2898. doi:10.1158/1538-7445.AM2014-2898
Abstract 2906: An effective anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer and its underlying mechanisms
Authors: Wu Han-Chung , Chi Yi-Hsuan , Liao Mei-Ying 
Published: May 2015

Abstract
Epithelial cell adhesion molecule (EpCAM) is known to be overexpressed in epithelial cancers associated with enhanced malignant potential, particularly colorectal carcinoma (CRC) and head and neck squamous cell carcinoma (HNSCC). However, it is yet to be determined whether targeting EpCAM can directly inhibit the progression of malignance. Here, we have generated six novel monoclonal antibodies (mAbs) against EpCAM; these antibodies specifically bind to CRC and HNSCC cells, but not normal cells. One EpCAM mAb, EpAb2-6, was found to induce cancer cell apoptosis in vitro, inhibit tumor growth, and prolong the overall survival of mice with human colon or oral carcinoma xenografts. EpAb2-6 also increases the therapeutic efficacy of irinotecan, fluorouracil, and leucovorin (IFL) therapy in tumor-bearing mice. Subsequent analysis suggested that EpAb2-6 can potentially inhibit the growth and proliferation of tumorspheres. Investigation of the mechanism by which EpAb2-6 inhibits tumor growth revealed that EpAb2-6 inhibits tumor-necrosis-factor α converting enzyme (TACE/ADAM17) and γ-secretase activation and blocks EpCAM intracellular domain (EpICD) cleavage, thus preventing the nuclear localization of EpICD. Furthermore, EpAb2-6, which binds to positions in the EGF-II/TY domain of EpCAM, inhibits production of EpICD, thereby decreasing translocation of β-catenin into the nucleus and activation of p53 and p21 expression. Collectively, our results indicate that novel EpCAM mAbs can potentially be used for cancer-targeted therapy.
Citation Format: Han-Chung Wu, Yi-Hsuan Chi, Mei-Ying Liao. An effective anti-EpCAM antibody EpAb2-6 for the treatment of colon cancer and its underlying mechanisms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2906. doi:10.1158/1538-7445.AM2014-2906
Abstract 2907: Everolimus enhances the cytotoxic action of the immunotoxin, HA22, directed to CD22 on B-cell malignancies
Authors: Antignani Antonella , Pasetto Matteo , Choo Chris , Angelus Evan , Mathews Lesley , Guha Rajarshi , Shinn Paul , Ferrer Marc , Thomas Craig J. , Pastan Ira , Fitzgerald David J. 
Published: May 2015

Abstract
Recombinant immunotoxins, antibody-toxin fusion proteins, are therapeutic proteins designed as targeted anti-cancer agents. Clinical trials of immunotoxins directed to surface CD22 or mesothelin are ongoing with a 50% complete response rate in patients with refractory Hairy Cell Leukemia as well as dramatic responses in some patients with advanced mesothelioma. To identify agents that could improve clinical efficacy further, a screen of 500 approved or near-approved compounds (MIPE-4) was conducted, revealing everolimus as a potential enhancer of Pseudomonas exotoxin-based recombinant immunotoxins. When the immunotoxin HA22 (moxetumomab pasudotox), which targets CD22, was added to various B-cell lines, everolimus enhanced cytotoxicity by 2-10-fold. Kinetic analyses indicated that combinations of HA22 and everolimus (0.25 uM) accelerated the cessation of protein synthesis in Nalm-6 and CA46 cells compared to either agent alone. Likewise, in CellTiterGlo assays of cell viability, combinations of HA22 and everolimus resulted in a greater loss of ATP from cells. Western blot analysis of key survival proteins indicated an early loss of Mcl-1 in combination treatments. Additional experiments are ongoing to extend these observations with the goal of uncovering insights in the mechanism of synergy seen with these two compounds.
Citation Format: Antonella Antignani, Matteo Pasetto, Chris Choo, Evan Angelus, Lesley Mathews, Rajarshi Guha, Paul Shinn, Marc Ferrer, Craig J. Thomas, Ira Pastan, David J. Fitzgerald. Everolimus enhances the cytotoxic action of the immunotoxin, HA22, directed to CD22 on B-cell malignancies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2907. doi:10.1158/1538-7445.AM2014-2907
Abstract 2916: Childhood BMI is associated with risk of adult pancreatic cancer
Authors: Nogueira Leticia M. , Stolzenberg-Solomon Rachael , Gamborg Michael , Sørensen Thorkild , Baker Jennifer 
Published: May 2015

Abstract
The incidence and death rate for pancreatic cancer, the fourth leading cause of cancer death in the U.S., have been increasing. Excess weight through adulthood is one of the few modifiable risk factors for pancreatic cancer. Childhood obesity rates have increased more rapidly that adulthood obesity in the U.S, but its effects on pancreatic cancer risk are not clear.
Hence, the objective of this study is to test the hypothesis that childhood weight is associated with pancreatic cancer risk later in life.
We evaluated the association of body mass index (BMI) measured at ages 7-13 with risk of pancreatic cancer later in life in 288,423 children from the Copenhagen School Health Records Register who were born between 1930-1981. These data were linked with the Danish Cancer Registry to identify incident pancreatic cancer cases from 1977-2011. Follow-up ended on the date of pancreatic cancer diagnosis, death, emigration, 70th birthday, or December 31st 2010, whichever came first.
Hazard Ratios (HR) and 95% confidence intervals (CI) were calculated for age specific BMI z-scores using Cox proportional hazards stratified on birth cohort and gender. Restricted cubic splines analysis was used to test for linearity. There were 1163 pancreatic cancer cases during the 6,918,420 person-years of follow up. Childhood BMI was associated with pancreatic cancer risk in males and females. At age 10, for example, HR per one unit increase in BMI z-scores was 1.17 (CI: 1.08, 1.26). The observed association did not deviate from linearity.
Our results support the hypothesis that higher childhood body weight is associated with increased pancreatic cancer risk later in life.
Citation Format: Leticia M. Nogueira, Rachael Stolzenberg-Solomon, Michael Gamborg, Thorkild Sørensen, Jennifer Baker. Childhood BMI is associated with risk of adult pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2916. doi:10.1158/1538-7445.AM2014-2916
Abstract 2922: Prediagnostic smoking, alcohol intake, physical activity and survival after colorectal cancer diagnosis in Western European populations
Authors: Fedirko Veronika , Riboli Elio , Norat Teresa , Tjønneland Anne , Jenab Mazda 
Published: May 2015

Abstract
Background: Cigarette smoking, high intake of alcohol, and lack of physical activity are associated with increased colorectal cancer (CRC) risk, but little research has been conducted to investigate the association between these modifiable lifestyle factors and survival after CRC diagnosis.
Methods: Therefore, we prospectively assessed the association between smoking status and intensity, baseline alcohol intake, lifetime pattern of alcohol intake, physical activity and all-cause and CRC-specific death among 3,916 participants diagnosed with colorectal cancer (colon = 2,454, rectum = 1,462) between 1992 and 2008 in the EPIC cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs).
Results: There were 1,303 deaths, 1,039 (80%) due to CRC. Mean follow-up after CRC diagnosis was 4 years. In multivariable analysis, current vs. never smokers had an increased risk of all-cause death (HR = 1.22, 95% CI: 1.04-1.44). Greater intensity of smoking (26+ cigarettes per day) was associated with almost a doubling in the risk of all-cause death when compared with never smokers (HR = 1.75, 95% CI: 1.12-2.73). Alcohol consumption was not statistically significantly associated with survival (HR = 1.00, 95% CI: 0.98-1.02 per 6 g per day), however former heavy drinkers had an increased risk of all-cause death (HR = 2.68, 95% CI: 1.13-6.39). Total physical activity was not statistically significantly associated with CRC survival. Additional subgroup analyses were conducted by sex, age at diagnosis, cancer stage and grade, location of tumor, time between blood collection and cancer diagnosis, year of diagnosis, follow-up period, and body mass index. Results for CRC-specific death were similar to those reported for all-cause death.
Conclusions: Our preliminary results suggest that cigarette smoking and being a former heavy drinker before cancer diagnosis are associated with worse survival among Western European patients with CRC, but further research is needed to confirm these results.
Citation Format: Veronika Fedirko, Elio Riboli, Teresa Norat, Anne Tjønneland, Mazda Jenab, on behalf of the EPIC CRC Working Group. Prediagnostic smoking, alcohol intake, physical activity and survival after colorectal cancer diagnosis in Western European populations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2922. doi:10.1158/1538-7445.AM2014-2922