bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1227: Macrophage depletion enhances the anticancer efficacy of eribulin mesylate in mice bearing syngeneic tumors.
Authors: Albu Diana I. , Littlefield Bruce A. , Woodall-Jappe Mary 
Published: August 2014

Abstract
Recent reports utilizing the MMTV-PyMT spontaneous model of breast cancer established that inhibition of macrophage recruitment to the tumors resulted in increased anti-cancer activity of paclitaxel. Eribulin mesylate (Halaven®) is a non-taxane microtubule-dynamics inhibitor recently approved for third line clinical use in patients with heavily pretreated metastatic breast cancer, based upon a statistically significant increase in median overall survival (OS) compared to treatment of physician's choice. In the present study we investigated whether systemic depletion of macrophages would enhance eribulin anti-tumor efficacy. In the subcutaneous Lewis lung carcinoma (LLC) syngeneic murine tumor model, we found that macrophage depletion via liposomal clodronate enhanced eribulin inhibition of tumor growth. Current studies are investigating the mechanism(s) of this activity.
Citation Format: Diana I. Albu, Bruce A. Littlefield, Mary Woodall-Jappe. Macrophage depletion enhances the anticancer efficacy of eribulin mesylate in mice bearing syngeneic tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1227. doi:10.1158/1538-7445.AM2013-1227
Abstract 1230: Impact of apheresis (Aph) on number and function of lymphocytes in cancer patients (pts).
Authors: Gulley James L. , Heery Christopher R. , Steinberg Seth , Marte Jenn , Madan Ravi A. , Schlom Jeffrey 
Published: August 2014

Abstract
It has been suggested that Aph, used for Sipuleucel-T, may negatively affect the OS of cancer pts by removing circulating lymphocytes and diminishing host immunity. We explored data from prior clinical trials in which pts had Aph or simple phlebotomy for evidence to support or contradict this.
We examined data from cancer pts on clinical trials who had Aph (n=64) or only peripheral blood draws (n=90) as controls for immune analysis. As the 1° functional analysis, we evaluated the impact of Aph on the flu specific T-cells using ELISPOT. We also evaluated the impact on absolute lymphocyte count (ALC), T cells (CD3, CD4, CD8, and CD4:CD8 ratio). ELISPOT was expressed as number of cells/spot (i.e. 1/10,000 would be expressed as 10,000). For all parameters, baseline (pre) values were compared to post-treatment (post) values using a Wilcoxon signed rank test. A large two-tailed p-value would indicate no significant change in values. Findings from smaller groups who underwent Aph multiple times are described.
In the Aph group, the median age was 63 (range 38-82); 92% male. Comparing the pre and post values within the groups, with each pt as its own control, there was no significant difference when comparing ELISPOT, ALC, and T cells (Table). 13 pts had a 3rd Aph with ELISPOT; 7 had improved responses to flu with an even distribution around no change. 29 pts underwent &gt;2 Aph (range 3-19, median 4), 20 with matched ALC and 20 with T cell values. There was a trend toward a slight decrease (&lt;10%) in ALC and T cell subsets. These findings supported the statistical analysis, which identified no consistently positive or negative change in pts who received Aph.
This analysis indicates there is no difference in the number and function of immune cells post Aph in cancer pts. This data provides evidence that Aph inflicts negligible effects on a pts immune system, rejecting the hypothesis that pts immune competence is impacted by the procedure in a meaningful way.
Post minus pre valuesELISPOT (n = 64)ALC (n = 52)CD3 (n = 36)CD4 (n = 36)CD8 (n = 36)CD4:CD8 ratio (n = 15)Aph groupDifference Pre vs PostMean500.906−0.02133.72102.7219.420.51Median0.000.0097.5063.5020.000.23P value1.000.780.0360.0240.560.0045InterpretationNo changeNo changeTrend IncreaseTrend IncreaseNo changeSignificant IncreaseNon-Aph group N = 90Difference Pre vs PostMean500.600Median0.00P value1.00
Citation Format: James L. Gulley, Christopher R. Heery, Seth Steinberg, Jenn Marte, Ravi A. Madan, Jeffrey Schlom. Impact of apheresis (Aph) on number and function of lymphocytes in cancer patients (pts). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1230. doi:10.1158/1538-7445.AM2013-1230
Abstract 1241: Targeting the IL-13 receptor alpha 2 with novel antibody-drug conjugates for the treatment of cancer.
Authors: Ma Dangshe , Zhang Haige , Jin Fang , Charati Manoj , Khandke Kiran , Lucas Judy , Follettie Max , Tumey L. Nathan , Gerber Hans-Peter , Tchistiakova Lioudmila , Sapra Puja 
Published: August 2014

Abstract
The IL-13 receptor alpha 2 (IL-13Rα2) is a transmembrane protein that is highly expressed on several cancers including glioblastoma, ovarian, pancreatic cancers. It can internalize after binding to its ligand IL-13 or in response to ligation with an antibody. In addition, we have discovered that IL-13Rα2 is up-regulated in tumor cell lines that are resistant to chemotherapeutic drugs. These properties make IL-13Rα2 an attractive target for antibody-drug conjugate (ADC), an emerging modality of molecularly targeted cancer therapies. A humanized monoclonal antibody, hAB08 with an affinity of 0.17 nM to the soluble recombined hIL-13Rα2, was conjugated with two novel microtubule inhibitors (MTIs), MTI1 and MTI2, developed by Pfizer. In vitro cytotoxicity of the conjugates was tested against IL-13Rα2 positive and negative cell lines. These conjugates were effective against the IL-13Rα2 positive cell lines (PC3MM2 and A375), having an IC50 ranging from 1.1 to 3.8 ng Ab/mL. However, both of the ADCs were not active against the IL-13Rα2 negative H460 cell line. When treating mice with established human PC3MM2 and A375 tumors, these conjugates were efficacious at 3 mg/kg in reducing tumor growth. In the PC3MM2 model, treatment with hAB08-MTI1 and hAB08-MTI2 resulted in 5 out of 8 or 3 out of 8 animals without measurable tumors at Day 76, respectively. In contrast, the vehicle control group and control ADC (hIgG8.8-MTI1 and hIgG8.8-MTI2) groups were terminated at Day 15, 15, 19 due to the large size of tumors, respectively. These in vitro and in vivo results demonstrate potent antitumor activities of hAB08-MTI1 and hAB08-MTI2 against IL-13Rα2 positive tumors. The findings support the development of novel hAB08-MTI1 or hAB08-MTI2 ADCs as a molecularly targeted therapy for cancer patients that are resistant to standard chemotherapy.
Citation Format: Dangshe Ma, Haige Zhang, Fang Jin, Manoj Charati, Kiran Khandke, Judy Lucas, Max Follettie, L. Nathan Tumey, Hans-Peter Gerber, Lioudmila Tchistiakova, Puja Sapra. Targeting the IL-13 receptor alpha 2 with novel antibody-drug conjugates for the treatment of cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1241. doi:10.1158/1538-7445.AM2013-1241
Abstract 1244: Phosphatidylserine-targeting antibody reactivates tumor immunity and destroys tumor vasculature in mice.
Authors: Yin Yi , Huang Xianming , Ye Dan , Thorpe Philip 
Published: August 2014

Abstract
The immunosuppressive lipid, phosphatidylserine (PS), becomes exposed on tumor blood vessels and tumor cells responding to therapy. The exposed PS contributes to the immunosuppressed tumor microenvironment. Bavituximab is a phosphatidylserine (PS)-targeting antibody that is being combined with chemotherapy in clinical trials in cancer patients. Here, we tested the hypothesis that innate immunity against cancer can be elicited by combining chemotherapy with a monoclonal antibody that indirectly binds exposed phosphatidylserine (PS). We used a murine version of bavituximab, 2aG4, plus docetaxel to treat prostate tumors in mice. Combination treatment markedly retarded tumor growth, prolonged survival times and delayed progression to androgen-independent disease. Antibody treatment reduced the presence of myeloid-derived suppressor cells (MDSCs) in the tumors and caused macrophages to repolarize from the immunosuppressive, proangiogenic M2-like state into a tumoricidal M1-like state. The reactivated macrophages destroyed antibody-coated tumor vasculature and tumor cells. Addition of 2aG4 to MDSCs in vitro caused them to differentiate into M1-like macrophages and DCs. Thus, PS-targeting antibodies appear to reactivate innate immunity in tumors resulting in tumor growth inhibition.
Citation Format: Yi Yin, Xianming Huang, Dan Ye, Philip Thorpe. Phosphatidylserine-targeting antibody reactivates tumor immunity and destroys tumor vasculature in mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1244. doi:10.1158/1538-7445.AM2013-1244
Abstract 1246: Development of an agonistic antibody against the human T-cell costimulatory receptor CD27 as a potential immunotherapeutic tool.
Authors: van Eenennaam Hans , Veraar Elise , Mulder Winfried , Bastiaanssen Ellen , Driessen Lilian , Lutje Hulsik David , Vink Paul , van der Horst Gerda , Xiao Yanling , Borst Jannie , van Elsas Andrea 
Published: August 2014

Abstract
Immunotherapy of cancer has reached a mature and exciting stage. Clinical activity of monoclonal antibodies (mAb) against the T-cell inhibitory receptors CTLA-4 and PD-1 indicate that cancer patients often have latent tumour-specific T cells that can be mobilized by blocking these receptors. Activation of the T-cell costimulatory receptor CD27, a member of the TNF receptor family, provides another opportunity to promote cytotoxic T cell (CTL)-based anti-tumor immunity. To generate agonistic mAb against human (h)CD27, we used our unique B-cell selection and immortalization technology. Various novel anti-hCD27 mAb were generated and tested for their agonistic properties. We used in vitro read-out systems detecting CD27 (co-)stimulatory function on the basis of NF-κB activity, T cell division and survival. One mAb hCD27.15 (KD ∼1 nM), induced CD27 receptor activation (EC50 ∼1 nM) without the need of cross-linking. Similar to its natural ligand CD70, our hCD27.15 mAb showed bona fide costimulatory properties. hCD27.15 strongly promoted CD8+ T cell expansion under conditions of suboptimal T-cell receptor (TCR) stimulation. hCD27.15 did not stimulate T cell function in absence of TCR engagement. hCD27.15 mAb demonstrated different binding kinetics and a unique epitope, compared to other antibodies that depend on cross-linking to activate CD27. Importantly, hCD27.15 retained its agonistic properties when expressed as a human IgG1 or IgG4 chimera. hCD27.15 was shown to bind and activate primate CD27 with similar potency, providing a rationale for pre-clinical safety testing. In conclusion, to our knowledge we have developed the first mAb to hCD27 that mimics ligand function without the need for cross-linking. Data from mouse models strongly support the application of CD27 agonism to enhance CTL-based anti-tumor immunity, by promoting the generation and survival of CTL, as well as their memory function. We propose therefore that hCD27.15 mAb is a promising tool for cancer immunotherapy.
Citation Format: Hans van Eenennaam, Elise Veraar, Winfried Mulder, Ellen Bastiaanssen, Lilian Driessen, David Lutje Hulsik, Paul Vink, Gerda van der Horst, Yanling Xiao, Jannie Borst, Andrea van Elsas. Development of an agonistic antibody against the human T-cell costimulatory receptor CD27 as a potential immunotherapeutic tool. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1246. doi:10.1158/1538-7445.AM2013-1246
Abstract 1248: Intralesional injection with PV-10 induces a systemic anti-tumor immune response in murine models of breast cancer and melanoma.
Authors: Pilon-Thomas Shari A. , Weber Amy , Kodumudi Krithika , Kuhn Lisa , Toomey Paul , Sarnaik Amod 
Published: August 2014

Abstract
PV-10 is a 10% solution of Rose Bengal that is currently being examined as a novel cancer therapeutic. In melanoma patients, intralesional injection (IL) of PV-10 has led to regression of injected lesions as well as distant metastases. In this study, we examined the efficacy and potential immune mechanism of PV-10 treatment in murine models of breast cancer and melanoma. In BALB/c mice bearing MT-901 breast cancer, injection of PV-10 led to regression of injected and untreated contralateral subcutaneous lesions (p&lt;0.05 compared to IL-PBS-treated mice). A significant increase in survival was observed in mice treated with PV-10. To examine immune response, MT901-specific IFN-gamma production and cytotoxicity were measured in splenocytes collected from mice treated with IL-PBS or IL-PV-10. MT901-bearing mice treated with IL-PV-10 demonstrated enhanced IFN-gamma production (992 ± 453 pg/ml) compared to splenocytes from PBS-treated mice (174 ± 105, p&lt;0.05). In addition, a significant increase in lysis of MT-901 cells by T cells after PV-10 treatment was observed (p&lt;0.01 compared to PBS-treated mice). No lysis of irrelevant CT-26 cells was detected. In a murine model of melanoma, B16-F10 cells were injected into C57BL/6 mice to establish one subcutaneous tumor and multiple lung lesions. Treatment of the subcutaneous lesion with a single injection of IL-PV-10 led to regression of the injected lesion as well as distant B16 melanoma lung metastases. In B16-bearing mice, treatment with IL-PV-10 led to the induction of T cells that produced IFN-gamma in response to B16 tumors but not irrelevant tumor (p&lt;0.05) and demonstrated specific lysis of B16 (p&lt;0.01 compared to T cells isolated from PBS-treated mice). In total, these studies support the induction of tumor-specific T cell-mediated immunity after single treatment with IL-PV-10 in multiple histologic subtypes. The immune mechanism of PV-10 ablation in cutaneous melanoma patients is currently under investigation at our institution.
Citation Format: Shari A. Pilon-Thomas, Amy Weber, Krithika Kodumudi, Lisa Kuhn, Paul Toomey, Amod Sarnaik. Intralesional injection with PV-10 induces a systemic anti-tumor immune response in murine models of breast cancer and melanoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1248. doi:10.1158/1538-7445.AM2013-1248
Abstract 1249: Potent immunomodulatory effects of lenalidomide enhance the effect of a therapeutic vaccine against established lymphoma in mice .
Authors: Sakamaki Ippei , Kwak Larry W. , Cha Soung-chul , Yi Qing , Lerman Beatrisa , Chen Jian , Surapaneni Sekhar , Bateman Scott , Qin Hong 
Published: August 2014

Abstract
Lenalidomide is an effective therapeutic agent with direct inhibitory effects on malignant B- and plasma cells and immunomodulatory effects on the T cell activation. The dual function of lenalidomide makes it an appealing candidate for combination with other novel cancer agents. We investigated the immune stimulatory effects of lenalidomide, administrated to mice in doses which provided comparable pharmacokinetics to human patients, on the potency of a novel fusion DNA lymphoma vaccine. The combination protected mice from lethal challenge with syngeneic A20 murine lymphoma, resulting in significantly improved survival compared with vaccine or lenalidomide alone and induced immune memory. In vivo depletion experiments demonstrated a requirement for effector CD8+ and CD4+ T cells. Surprisingly, lenalidomide alone was associated with reduced numbers of systemic immune suppressive cells (MDSC/Treg) in tumor-bearing, but not naïve mice, an effect that was independent of simple tumor burden reduction. Finally, the combination of lenalidomide and vaccine produced significantly improved survival in mice with 7 day established tumors. These results demonstrated the dual effect of lenalidomide on enhancing antigen-specific T-cell immunity and a novel mechanism of action reversing tumor-induced immune suppression, which makes it ideal for combination with vaccines as an immune adjuvant.
Citation Format: Ippei Sakamaki, Larry W. Kwak, Soung-chul Cha, Qing Yi, Beatrisa Lerman, Jian Chen, Sekhar Surapaneni, Scott Bateman, Hong Qin. Potent immunomodulatory effects of lenalidomide enhance the effect of a therapeutic vaccine against established lymphoma in mice . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1249. doi:10.1158/1538-7445.AM2013-1249
Abstract 125: Hematological cancer incidence among semiconductor workers.
Authors: Lee Kyoungho , Han Joohee , Kim Kwansick , Kim Soo-Geun 
Published: August 2014

Abstract
Background/objective. There has recently been such great interest in cancer incidence among the semiconductor workers. Therefore, an epidemiological study was conducted to figure out the cancer incidence rate among semiconductor workers and potential factors affecting cancer.
Methods. The study was performed for the semiconductor workers employed from 1999 to 2008, and the total number of workers in a cohort was 56,283 who employed for over one month. Cancer incidence rate was analyzed by departments, divisions, job titles, gender, age, viral hepatitis and working duration. We compared the incidence of hematological cancer in this cohort with that expected on the basis of cancer incidence in the general population.
Results. Overall, the standardized incidence rate (SIR) for workers indicates 0.76 (95% CI: 0.66-0.86) compared to general population data. In particular, the rate for leukemia was 0.86(0.50-1.47) in the total. Non-Hodgkin's lymphoma was observed high SIR which was not statistically significant among female assembly workers(2.42, 95% CI: 0.78-7.49), whereas in office workers were significant high (5.23, 95% CI: 1.31-20.92). We also found that the hepatitis virus affected in female workers (7.69, 95% CI: 1.08-54.60).
Conclusions. We concluded that the SIR for non-Hodgkin's lymphoma among female workers is high because of personal factors and additional research works are considered for some confounder factors. Epidemiological study based on a constant, long-term prospective cohort is required for the future studies.
Citation Format: Kyoungho Lee, Joohee Han, Kwansick Kim, Soo-Geun Kim. Hematological cancer incidence among semiconductor workers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 125. doi:10.1158/1538-7445.AM2013-125
Abstract 1259: Murine HLA-restricted CD4+ T cell lines as source of high affinity TCRs specific for the human breast cancer-associated tumor antigen NY-BR-1.
Authors: Gardyan Adriane , Osen Wolfram , Eichmüller Stefan B. , Zoernig Inka , Jaeger Dirk 
Published: August 2014

Abstract
Out of all malignancies, breast cancer is the second most common cancer worldwide and the leading cause of cancer death in females. Passive immunization approaches such as adoptive transfer of TCR-transduced autologous T cells specific for tumor associated antigens, provide an innovative strategy for cancer immunotherapy. The differentiation antigen NY-BR-1 has been described to be expressed in 60% of all invasive mammary carcinomas. Since NY-BR-1 protein levels are highly elevated in malignant breast tissues compared to healthy breast tissue, NY-BR-1 might represent a suitable target antigen for T cell based immunotherapy approaches against breast cancer. Successful immunological eradication of tumors depends on the presence of activated tumor antigen-specific CD4+ effector T cells as documented by numerous reports. Therefore, NY-BR-1 was screened for the presence of CD4+ T cell epitopes using HLA-transgenic mice immunized with a NY-BR-1-encoding expression plasmid and subsequent ex vivo analysis of the NY-BR-1-specific T cell responses against a synthetic peptide library covering the entire NY-BR-1 protein. Stable CD4+ T cell lines specific for six newly identified epitopes could be established from peptide-immunized DRB1*0301 and HLA-DRB1*0401-transgenic mice and HLA-DR-restriction of the cell lines was confirmed on peptide loaded T2/DR3 and T2/DR4 target cells. Next, natural processing of the epitopes identified in HLA transgenic mice will be tested in the human system using human HLA-matched cells lines infected with NY-BR-1 encoding adenovirus as targets for recognition by the murine NY-BR-1-specific CD4+ T cell lines. Clinical relevance of the newly identified NY-BR-1-specific epitopes will be investigated by screening of blood samples from NY-BR-1+, HLA-matched breast cancer patients for the presence of cognate CD4+ T cells. High affinity TCRs from NY-BR-1 specific CD4+ T cells will be sequenced and subsequently used to generate autologous TCR-transduced T cell lines ready for adoptive transfer of breast cancer patients
Citation Format: Adriane Gardyan, Wolfram Osen, Stefan B. Eichmüller, Inka Zoernig, Dirk Jaeger. Murine HLA-restricted CD4+ T cell lines as source of high affinity TCRs specific for the human breast cancer-associated tumor antigen NY-BR-1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1259. doi:10.1158/1538-7445.AM2013-1259