bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1572: Development of novel and effective therapeutic peptide vaccines against HPV-induced tumors
Authors: Barrios Kelly , Celis Esteban 
Published: August 2012

Abstract
Our main goal is to generate effective therapeutic peptide-based vaccines against viral-induced cancers. We are first focusing on human papillomavirus (HPV) induced malignancies because of their high worldwide prevalence (e.g., cervical carcinoma and head & neck cancer). We have used an HPV-induced mouse cancer model to test vaccines composed of a CD8 T cell peptide epitope administered with potent adjuvants designed to generate vast numbers of high avidity cytotoxic T lymphocytes specific for the HPV16-E7 antigen. One vaccination strategy (TriVax) consists of intravenous administration of synthetic peptide HPV16-E749-57 administered together with a Poly-IC (a TLR3 agonist) and anti-CD40 monoclonal antibody (≥CD40 mAb) while the second more simple strategy (BiVax) comprises of peptide plus Poly-IC. We assessed both the immunogenicity and therapeutic anti-tumor effects of both vaccination strategies. While TriVax was clearly more immunogenic than BiVax, both vaccines showed remarkable anti tumor effects against the HPV16-E7 expressing tumors TC-1 and C3.43. In addition, we will present results suggesting that some peptides such as HPV16-E749-57 can be highly immunogenic in the absence of CD40 costimulation (i.e., in the BiVax format), due to their capacity to form complexes with Poly-IC. We hypothesize that peptide/Poly-IC complexes are highly immunogenic because they are targeted to professional antigen-presenting cells via some type of scavenger receptor specialized in capturing nucleic acids.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1572. doi:1538-7445.AM2012-1572
Abstract 1573: MAGED4B drives oral carcinogenesis and is a promising peptide vaccine target for the treatment of oral squamous cell carcinoma
Authors: Lim Kue Peng , Gan Chai Phei , Chong Chan Eng , Zain Rosnah Binti , Abraham Mannil Thomas , Rahman Zainal Ariff Abdul , Teo Soo-Hwang , Gutkind J Silvio , Patel Vyomesh , Ponniah Sathibalan , Cheong Sok Ching 
Published: August 2012

Abstract
MAGED4B is a member of the Melanoma Antigen Gene (MAGE) family. We demonstrated that MAGED4B is over-expressed in more than 50% of oral squamous cell carcinoma (OSCC) tissues and that the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines over-expressing MAGED4B exhibited an increase in cell growth both in vitro and in vivo, and were significantly more resistant to UV-induced apoptosis compared to control cells, suggesting a role for MAGED4B in modulating cell death. Further, MAGED4B also promoted cell migration. MAGE proteins are good targets for cancer immunotherapy as they are highly immunogenic. We identified and synthesized MAGED4B peptides that were HLA-A2- specific and tested the ability of these peptides to generate an anti-tumour response using PBMCs from OSCC patients and healthy individuals. Firstly, the PBMC samples obtained from patients and healthy individuals were tested for HLA-A2 expression. Positive samples were analyzed for peptide-specific stimulation of IFN-γ and granzyme secretion ex-vivo via ELISPOT assay. Dendritic cells pulsed with these peptides were used to stimulate PBMC cultures, and were studied for IFN-γ and granzyme secretion. In parallel, the binding of the peptides to the MHC-Class I molecule was determined by the binding assay. Further, the ability of these bound peptides to interact with T cells was measured by the dimer assay. We demonstrated that all the peptides have good binding capacity with the MHC-Class I molecules. Moreover, the binding of these peptides on MHC-Class I molecules could attract and further interact with T cells. Notably, the PBMC stimulated once with peptide-pulsed dendritic cells or twice with peptide and peptide-pulsed dendritic cells showed peptide-specific cytotoxic activity against MAGED4B-expressing OSCC cell lines. In summary, we first demonstrated that MAGED4B drives oral carcinogenesis and second, showed that MAGED4B-specific peptides are apable of inducing anti-tumour specific immune responses. Taken together, this indicates that MAGED4B could be a promising peptide vaccine target for the treatment of OSCC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1573. doi:1538-7445.AM2012-1573
Abstract 1575: A dual immunostimulatory strategy for pancreatic cancer treatment: MUC1 cytoplasmic tail peptide therapeutic vaccine with adjuvant TLR3 agonist poly(I:C12U)
Authors: Fink Darci M. , Tremayne Jarrod , Bunt Stephanie K. , Hollingsworth Michael A. 
Published: August 2012

Abstract
Immunotherapy directed against MUC1, a membrane-bound mucin, may be a treatment option for pancreatic cancer patients. MUC1 is overexpressed and differentially glycosylated and phosphorylated by pancreatic cancer cells and is thus a candidate antigenic target for a therapeutic vaccine. Vaccination studies using full length MUC1 cytoplasmic tail (MUC1-CT) peptide in vivo showed an increase in median survival of C57BL/6 mice transgenic for and immunologically tolerant to MUC1 (MUC1.Tg) challenged with a syngeneic murine pancreatic tumor cell line (Panc02.MUC1) as compared to nonvaccinated controls. In a recent study, we employed an immunostimulatory adjuvant in concert with MUC1-CT peptide to improve immune system mobilization in MUC1-tolerant animals thereby enhancing the therapeutic effect of vaccination. The chosen adjuvant, poly(I:C12U), is a clinically tested GMP-grade dsRNA molecule capable of activating Toll-like receptor 3 (TLR3) present on endocytic vesicles in antigen presenting cells (APC). Agonizing TLR3 induces dendritic cell maturation in vitro and in vivo, leading to increased antigen presentation and cytokine production that prompt an antigen-specific T cell response. We hypothesized that a dual immunostimulatory strategy pairing TLR3 agonist-mediated APC activation with tolerance-breaking MUC1-CT antigen-directed vaccination would lead to directed destruction of pancreatic cancer cells and improved overall survival. Treatment with poly(I:C12U) alone, peptide alone, or gemcitabine alone improved survival in this model system; however, co-administration of poly(I:C12U) and peptide did not provide additive or synergistic benefit in this protocol.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1575. doi:1538-7445.AM2012-1575
Abstract 1577: Lactobacilli secreting a tumor antigen and IL15 activates neutrophils and dendritic cells and generates cytotoxic T lymphocytes against cancer cells
Authors: Esuvaranathan Kesavan , Kandasamy Matheswaran , Bay Boon Huat , Lee Yuan Kun , Mahendran Ratha 
Published: August 2012

Abstract
Introduction and Objective Lactobacillus rhamnosus GG (LGG) are lactic acid bacteria, which were found to be better than BCG at inducing cell death in human bladder cancer cell lines. This study compares both LGG and BCG in vivo in an orthopic model and further evaluates the potential of recombinant LGG to induce a directed anti-tumor response. Methods MB49-PSA (murine bladder cancer cells secreting human PSA) cells were implanted orthotopically in C57BL/6 mice and either LGG or BCG was instilled weekly for 6 weeks. Tumor cure rates were noted and an immnohistochemical examination was performed on the tumors. The human prostate specific antigen (PSA) PSA was cloned into pLP500-slpAp vector under the control of S-layer promoter of L. acidophilus. The murine IL-15 cDNA minus its termination codon was cloned upstream of the PSA protein sequence. Lactobacilli were transformed with the plasmids to generate LGG-IL15-PSA, LGG-PSA and LGG-S (pLP500-slpAp) respectively. PSA and IL15 secretion was 16-19 ng/2x109 CFU/ml. Bone marrow cells were isolated from the tibia and femur of 8-10 weeks old female C57BL/6 mice. Neutrophils were isolated by positive selection with anti-Ly6G microbead kit (Miltenyi Biotech, Germany). To generate DCs, bone marrow derived cells were cultured for 9 days in media with 40ng/ml of GM-CSF (BD Bioscience) which was replaced every other day. Neutrophils and DC were exposed to the recombinant LGG for 2h and used to stimulate T cells to generate CTL against the murine bladder cancer cell lines expressing PSA (MB49-PSA). Results LGG was as effective as BCG in the mice. Analysis of tumors after repeated weekly LGG instillations showed increased infiltration of neutrophils and macrophages into the tumor mass after therapy. In vitro, recombinant LGG activated neutrophils (elevated MHC class I expression) induced DC maturation (increased expression of CD86, CD80, CD40, MHC II and CD83), T cell proliferation and PSA specific cytotoxic T lymphocytes (CTL) activity. Activated DC were more efficient than activated neutrophils in inducing T cell IL2 and IFNα production. DC activated with LGG for 2 h or with LGG treated neutrophils were re-isolated and plated with naïve T cells for 5 days to generate PSA specific T cells. Then PSA secreting or control MB49 cells were added to the wells. IL15 enhanced DC generation of CTL. Conclusions Intravesical instillation of LGG cured mice of tumors. LGG secreting tumor antigens and cytokines could be used to activate DC in vitro for DC therapy in patients or used as intravesical therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1577. doi:1538-7445.AM2012-1577
Abstract 1580: LL-37-mediates tumor antigen-specific-T cell expansion and tumor regression
Authors: Singh Manisha , Liu Chengwen , Lou Yanyan , Gregorio Josh , Conrad Curdin , Hwu Patrick , Overwijk Willem W. , Gilliet Michel 
Published: August 2012

Abstract
We previously showed that the endogenous antimicrobial peptide LL-37, when coupled with self DNA, acts as a TLR-9 agonist and activates plasmacytoid dendritic cells (pDC) leading to type I IFN production. As tumor contains many dying cells releasing self DNA, we investigated whether intra-tumoral injection of LL-37 induces anti-tumor immunity through pDC activation. Mice bearing established subcutaneous B16-OVA melanoma were injected intratumorally with LL-37. LL-37 was found to induce IFN-γ expression in treated tumors. Furthermore, LL-37 induced an activation and expansion of OVA-antigen-specific CD8 T cells in draining lymph nodes as well as the tumor micro environment. This process was associated with delay in tumor growth. These findings suggest that LL-37 could induce anti-tumor immunity and provide a promising strategy for melanoma immunotherapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1580. doi:1538-7445.AM2012-1580
Abstract 1581: Identification of novel HLA-restricted T-cell epitopes specific for the breast cancer-associated tumor antigen NY-BR-1
Authors: Gardyan Adriane , Osen Wolfram , Jesiak Maria , Zörnig Inka , Jaeger Dirk , Eichmueller Stefan B. 
Published: August 2012

Abstract
Out of all malignancies, breast cancer resembles the most common malignant caner type (26%) of women in the western world and the second most frequent cancer related cause of death (15%) in women. Efficient treatment options are available for early stage breast cancers yielding five year survival rates of up to 85%, however for metastasized breast cancer types, five year survival rates are resided at much lower levels (20%) and therapy options are very limited. It is therefore of great importance to establish innovative therapy strategies which will affect the late stage breast cancer tumors. Immunotherapy approaches, particularly adoptive T cell transfer, constitute an attractive strategy to develop new therapy options for metastasized mammary carcinomas. The differentiation antigen NY-BR-1 was found to be expressed on mRNA level in breast tissue, testis, prostate, and most notably in 80% of tested breast cancers. Among normal tissues, expression of the NY-BR-1 protein was present solely in ductal epithelium of the breast. Compared to healthy breast tissue NY-BR-1 protein levels are highly elevated in invasive breast tumors and their corresponding metastasis. Thus, NY-BR-1 can be considered as a breast cancer associated tumor antigen that might represent a suitable target antigen for T cell based immunotherapy approaches. The main focus of this project is to identify novel HLA-restricted T cell epitopes that could be used in clinical trials. Therefore, various HLA-transgenic (tg) mouse strains (DR4tg, DR3tg and HHDtg mice), were immunized with the NY-BR-1- encoding expression plasmid pcDNA3.1-NY-BR-1 followed by ex vivo analyses of the NY-BR-1-specific T cell responses with a synthetic peptide library covering the entire NY-BR-1 protein. Applying this strategy, four potential HLA-DRB1*0301 restricted epitopes and three HLA-DRB*0401 restricted candidate epitopes could be determined. The relevance of these new epitopes for the human system will be analyzed by screening of PBMCs from tumor patients and healthy donors for the presence of cognate T cells. Such T cells will be expanded and used as donors for high affinity NY-BR-1-specific TCRs in order to establish autologous TCR-transduced T cells ready for adoptive transfer of breast cancer patients. Currently, blood-samples of NY-BR-1+ patients are being collected for subsequent in vitro analyses of HLA-restricted, NY-BR-1-specific T cell responses.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1581. doi:1538-7445.AM2012-1581
Abstract 1582: Therapeutic vaccine for pancreatic cancer
Authors: Khamar Bakulesh M. , Desai Nirav , Shukla Chandreswar 
Published: August 2012

Abstract
Cadi-05 (Heat killed mycobacterium w) is a potent TLR 2 agonist and induces pure potent Th1 response. In advanced Non small cell lung cancer, Cadi-05 is found to potentiate efficacy of chemotherapy (Paclitaxel + Cisplatin) with improvement in response rate and overall survival in a randomized controlled clinical trial. Cadi-05 is also a potent vaccine adjuvant for prophylactic vaccines providing faster, higher and sustained antibody titers in animals and humans. The therapeutic vaccine for pancreatic cancer, with killed pancreatic cancer cells as an antigen with Cadi-05 as an adjuvant was evaluated for its ability to induce cell mediated immune responses (by ELISPOT for IFN - α, IL-2 and Granzyme B) and effector function (By BrDu incorporation). The vaccine made using Mia PaCa-2 cell line induced cell mediated immune responses against the Mia PaCA-2 as well as against the other cell lines (Panc-1, ASPC-1, SW-1990). The vaccine also generated effector function of similar magnitude against all four cell lines. Effect of vaccine on tumor size and survival following intradermal immunization was also studied. For evaluating efficacy, C57BL/6 BYJ mice were injected Pan-02 cells (1x106) subcutaneously for developing pancreatic cancer model. At day 10 post tumor induction tumor size achieved was∼200-225 mm3. Mice were randomized to receive vaccine or placebo (18 mice each) on day 10. No other therapy was used in the experiment. In Vaccine arm tumor regression was seen in 61% of animals before progression. Tumor regression was not seen in placebo arm. Tumor progression was found to be slower in vaccinated animals with mean tumor size 35% and 59% of placebo arm on day7 (633 mm3 vs. 223 mm3) and day 12 (740 mm3 vs. 437 mm3) respectively resulting in survival benefit of 36% on day 40 following immunisation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1582. doi:1538-7445.AM2012-1582
Abstract 1583: New strategy for the identification of breast cancer antigens that induce therapeutic immune responses in tumor-bearing mice
Authors: Cohen Edward P. , Kim Tae Sung , Chopra Amla , O-Sullivan InSug 
Published: August 2012

Abstract
This study describes a unique strategy designed to identify breast cancer antigens (TAA) that induce therapeutic immune responses in tumor-bearing mice. In a mouse model, the strategy led to the identification of growth factor receptor-bound protein 10 (Grb10) as a newly identified TAA. Grb10 is a signal transduction molecule associated with multiple transmembrane tyrosine kinase receptors. It was discovered by comparing microarrays of cellular breast cancer vaccines highly enriched for cells that induced breast cancer immunity with non-enriched vaccines. The vaccines were prepared by transferring a cDNA expression library derived from SB5b cells, a breast cancer cell line derived from a neoplasm that arose spontaneously in the mammary gland of a C3H/He mouse into LM cells, a mouse fibroblast cell line. As the transferred cDNA integrates spontaneously into the genome of the recipient cells, replicates as the cells divide, and is expressed, the vaccine could be prepared from a little as 10 micrograms of tumor tissue. Relatively few cells in the transfected cell population, however, incorporated cDNA fragments that included genes specifying TAA. (The vast majority specified normal cellular constituents.) A unique strategy was developed, therefore, to enrich the vaccine for immunotherapeutic cells. Comparative microarrays of enriched and non-enriched vaccines resulted in the identification of twenty overrepresented genes. One, the gene for Grb10, was approximately 100-fold overrepresented. To determine if Grb10 in the enriched vaccine was partly responsible for its therapeutic benefits, the gene was incorporated into an expression plasmid that was then transfected into the fibroblast cell line, which was then used as a vaccine. Mice with established breast cancer treated solely by immunization with the fibroblasts modified to express Grb10 developed robust immunity to the breast cancer cells, which, in some instances, was sufficient to result in tumor rejection.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1583. doi:1538-7445.AM2012-1583
Abstract 1592: Silibinin inhibits UVB-induced DNA-damage and apoptosis by enhancing interleukin-12 expression in JB6 cells and SKH-1 mouse skin
Authors: Narayanapillai Sreekanth C. , Gu Mallikarjuna , Agarwal Chapla , Agarwal Rajesh 
Published: August 2012

Abstract
Ultraviolet-B (UVB) radiation plays a pivotal role in non-melanoma human skin cancers (NMSCs) by inducing cellular DNA damage, mutations and immunosuppression. Decades of research has demonstrated silibinin efficacy against UVB-induced skin carcinogenesis by regulating different molecular pathways in various cell lines and animal models; however, the role of silibinin in regulating interleukin-12 (IL-12), an immunomodulatory cytokine with the capacity to reduce UVB-induced DNA damage and apoptosis, has not been studied. Here, we report that UVB irradiation caused a dose- and time-dependent caspase 3 and PARP cleavage as well as apoptosis in JB6 cells. Addition of recombinant IL-12 or silibinin immediately after UVB significantly protected UVB-induced apoptosis in JB6 cells, and antibody-mediated blocking of IL-12 activity compromised the protective effect of both IL-12 and silibinin. In addition, both silibinin and IL-12 accelerated the repair of UVB-caused cyclobutane-pyrimidine dimers (CPDs) in JB6 cells. Additional studies confirmed that indeed silibinin causes a significant increase in IL-12 levels in UVB-irradiated JB6 cells as well as in the SKH-1 hairless mouse epidermis, and that similar to in vitro findings, silibinin topical application immediately after UVB exposure causes a very strong protection against UVB-induced TUNEL positive cells in epidermis possibly through a significantly accelerated repair of UVB-caused CPDs in skin epidermis. Together, these findings for the first time identify an important insight regarding the pharmacological mechanism wherein silibinin induces endogenous IL-12 in its efficacy against UVB-caused skin damages. Considering the fact that millions of people get constantly exposed to solar UVB radiation and live with persistent UVB-induced DNA lesions, the post-damage use of silibinin as an inducer of endogenous IL-12 in UVB-damaged human skin for the rapid repair of DNA damage could be a more practical and translational approach in reducing sunlight-caused damages in human skin which eventually lead to NMSCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1592. doi:1538-7445.AM2012-1592