bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Yupingfeng formula on anti-lung cancer via increasing immune memory in lung metastasis mouse model
Authors: Xu Zihang , Hu Jiemiao , Mitra Abhisek , Xia Xueqing , Zhu Shiguo , Li Shulin , Chen Xiao 
Published: January 2023

Abstract

Background
Yupingfeng(YPF), a classic herbal Chinese formula, has been used effectively for the cure and prevention of respiratory tract diseases. However, the role of YPF in lung cancer which is the most severe lung disease with no substantial therapies, remains unknown. Therefore, this study was carried out to elucidate the anti-lung cancer role of YPF in lung metastasis mouse model.

Methods
C57/BL6 mice were inoculated with LLC-Fgl2-GFP tumor cells intraosseously, then were divided into two groups. One group was YPF group, and the other was control group. YPF (580 mg/ml)or water were gavaged daily for 30 days. The primary leg tumor diameters were measured weekly. 31 days after inoculation the whole control group were euthanized due to excessive primary leg tumor burden. After India ink pulmonary perfusion of these mice, lots of lung metastases were observed. By striking contrast, the whole YPF group survived tumor free. We then used the same cell line and cell numbers to re-challenge these mice. 21 days after inoculation, the primary leg tumor could be detected. But 7 days later, the primary tumor started shrinking until tumor free again, suggesting YPF could activate the immune memory.

Results
The control group died of excessive primary leg tumor burden and lung metastases, while the YPF group were tumor free, and remained tumor free after being re-challenged with the same tumor cells. Our results suggested that YPF could significantly increase the survival rate of tumor bearing mice, compared to the control group.

In conclusion
These data support YPF can prolong mice’s survival time by enhancing immune memory in lung metastasis mouse model, which might be a possible mechanism for its therapeutic effect on tumor free mice.
Gene electrotransfer of plasmids encoding cytokines as an effective immunotherapy approach for melanoma
Authors: Heller Richard , Lundberg Cathryn M , Burcus Niculina , Edelblute Chelsea , Guo Siqi 
Published: January 2023

Abstract
Gene electrotransfer (GET) of plasmids encoding cytokines has been shown to generate a potent anti-tumor effect. Effective protocols have been developed delivering the plasmids directly into tumors. To obtain an effective immune response, it is critical to achieve a balance between transgene expression and tissue damage. GET is a reliable and effective physical method for in vivo delivery of plasmid DNA. It is particularly attractive for use in anti-cancer cytokine therapy as it does not incur the side effects associated with conventional protein cytokine therapy. Delivery of plasmids encoding cytokines directly to tumors has been shown by our lab and others to induce not only local immune response, but a systemic one as well. The positive responses were directly related to the ability to achieve the appropriate expression profile following delivery of the plasmid. Interestingly, the electrotransfer parameters were dependent on which cytokine was being delivered. For plasmid encoding IL-12 the correct parameters were 1300 V/cm and 100 us. For IL-15, the appropriate parameters were 600 V/cm and 5 ms. The procedure included injecting the plasmid DNA into established B16.F10 melanoma tumors of C57BL/6 mice and electric pulses applied three times over a one week period. To enhance this immune response, current work is further analyzing the immune response to determine if there is a marker that would indicate appropriate delivery of the plasmid. In addition, combination therapies are being explored to evaluate if the response could be augmented. A more complete understanding of the process and identifying other agents that could further augment this approach would be an important step.
Expression of a CD200-targeted chimeric costimulatory receptor enhances T cell effector function and adoptive immunotherapy of disseminated leukemia
Authors: Oda Shannon K , Daman Andrew W , Garcia Nicolas M , Tan Xiaoxia , Greenberg Philip D 
Published: January 2023

Abstract
CD200 (OX2) is an immunosuppressive surface protein upregulated in leukemia and other malignancies, with expression associated with inhibition of antitumor T cell responses and decreased overall survival of patients. Our lab has developed several T cell receptors (TCR) to target intracellular antigens upregulated in malignancies and we questioned if the efficacy of TCR gene therapy could be improved by co-opting CD200 inhibition with a CD200R-CD28 immunomodulatory fusion protein (IFP) that could potentially convert CD200/CD200R signaling into a costimulatory signal. T cells transduced with CD200R-CD28 exhibited enhanced proliferation, accumulation, and effector function in response to CD200+ target cells in vitro. Repeated restimulation with irradiated CD200+ tumor cells enriched the cells transduced with the IFP compared to wild type T cells. The CD200R-CD28 transduced T cells also exhibited enhanced killing of CD200+ compared to CD200− tumor cells. In adoptive therapy of disseminated leukemia, CD200R-CD28-transduced tumor-specific T cells eradicated otherwise lethal disease without a requirement for IL-2 administration to sustain in vivo persistence. Comparison of IFPs with CD28, 4-1BB, and CD28/4-1BB dual costimulatory domains suggested the CD28 signaling domain provides the most significant enhancement of anti-tumor activity. Additionally, modification of the IFP ectodomain length revealed the importance of optimizing the tumor-T cell distance for costimulatory signaling. Transduction of human primary T cells with the equivalent human IFP also resulted in increased proliferation and cytokine production in response to CD200+ leukemia cells, supporting clinical translation of this strategy.
Site-Specific Immunomodulators (SSIs) are novel immunotherapies for cancer
Authors: Zhang Monan Angela , Bosiljcic Momir , Kalyan Shirin , Anderson Rebecca , Bazett Mark , Luk Beryl , Wong Natalie , Mullins David W , Gunn Hal 
Published: January 2023

Abstract
The immune system recognizes and eliminates malignant cells, and maintains an intricate balance between immune activation and cancer. Historically, spontaneous tumor regression has been observed in some patients experiencing acute microbial infections. Building upon this, it was discovered that repeated subcutaneous injection of novel immunotherapies called Site-Specific Immunomodulators (SSIs), derived from killed bacteria known to cause infection in a particular organ or tissue, may be effective at treating cancer growing in the same site. We hypothesize that SSIs stimulate the body’s immune system to reverse immune suppression and dysfunction in the tumor microenvironment, enabling effective anti-cancer immune responses. To test this hypothesis, we evaluated the efficacy of a lung-specific SSI, QBKPN, in preclinical lung cancer models. Repeated subcutaneous administration of QBKPN significantly reduced lung tumor burden at day 16 post-inoculation (p&lt;0.0001) in the Lewis Lung Carcinoma model, improving median survival by 10 days (p&lt;0.005). Similar results were obtained using the aggressive and poorly-immunogenic B16 lung cancer model. Anticancer efficacy was associated with site-specific infiltration of newly recruited monocytes and neutrophils to the lung and mobilization of antigen presenting cells in the lung-draining lymph node. These data complement the positive results from our compassionate use clinical data, and provide strong evidence that SSIs may improve therapeutic outcomes for cancer patients. QBKPN is currently studied in a Phase 2a clinical trial of non-small cell lung cancer in collaboration with the BC Cancer Agency (Trial NCT02256852).
Delayed dosing intervals for quadrivalent human papillomavirus vaccine do not reduce antibody avidity
Authors: Brady Allison M , Walter Emmanuel B , Markowitz Lauri E , Unger Elizabeth R , Panicker Gitika 
Published: January 2023

Abstract
The quadrivalent HPV vaccine (HPV4) is recommended as a 3 dose schedule at 0, 2, 6 months for girls and boys. However, delays in dosing intervals frequently occur. We previously found that delayed intervals in girls resulted in similar or higher antibody (Ab) titers following series completion compared to the recommended schedule. We used archived specimens from that study to determine if delayed dosing intervals affected Ab avidity(a measure of how strongly Abs bind). The importance of avidity is unknown for HPV; however, avidity has been associated with clearance of other pathogens. We tested residual serum from 261 consenting healthy females, ages 9 through 18. Avidity index (AI) was determined just prior to and one month following dose 3 of HPV4 for each participant. Data were analyzed by dosing intervals, classified as:(1) on time dose 2 and 3, (2) delayed dose 2 and on time dose 3, (3) on time dose 2 and delayed dose 3, or (4) delayed dose 2 and 3. Avidity was measured using a modified multiplex ELISA, and AI was calculated as a ratio of IgG Ab bound in the treated and untreated sample. Overall, mean AI was highest for HPV16 and lowest for HPV6. As expected, AI did not differ between groups 1 & 3 or groups 2 & 4 after dose 2, however for most types mean AI was significantly higher for groups with delayed dose 2. Mean AI was higher post-dose 3 in all delayed dosing groups compared to the group 1 for all types. There was a weak to moderate correlation between overall AI and Ab titers for all types (HPV6r=0.27, HPV11 r=0.32, HPV16 r=0.25, HPV18 r=0.44; all p&lt;0.0001). Our findings suggest longer intervals between doses result in higher antibody avidity after a complete 3-doses series, providing further evidence that delayed dosing of HPV4 does not hinder the immune response.
Vaccination with Embryonic Stem Cells Protects against Lung Cancer
Authors: Richie Jamaal , Al-Rayyan Numan , Mitchell Robert , Eaton John , Yaddanapudi Kavitha 
Published: January 2023

Abstract
The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine embryonic stem cells (ESC). Naïve C57BL/6 mice were vaccinated with ESC along with a source of granulocyte macrophage-colony stimulating factor (GM-CSF). Vaccinated mice were protected against subsequent challenge with implantable Lewis lung carcinoma (LLC). ESC-induced anti-tumor immunity was not due to a non-specific “allo-response” as vaccination with allogeneic murine embryonic fibroblasts did not protect against tumor outgrowth. Vaccine efficacy was associated with robust tumor-reactive primary and memory CD8+ T effector responses, Th1 cytokine response, higher intratumoral CD8+T effector/CD4+CD25+Foxp3+ T regulatory cell ratio, and reduced myeloid derived suppressor cells in the spleen. Prevention of tumorigenesis was found to require a CD8-mediated cytotoxic T lymphocyte (CTL) response because in vivo depletion of CD8+ T lymphocytes completely abrogated the protective effect of vaccination. To overcome the limitations of using whole ESC as a vaccine we modified our vaccination approach using exosomes derived from ESC. Our preliminary results thus far indicate that ESC-derived exosomes as a vaccine is effective against implantable lung tumors in mice. Further refinement of this novel vaccine strategy and identification of shared ESC/tumor antigens may lead to immunotherapeutic options for lung cancer patients and, potentially represent a step toward the development of prophylactic cancer vaccines.
Production of DNA, Protein and DNA/Protein vaccines against Leishmania infantum and L.tropica
Authors: Yazar Suleyman , Aksit Abdussamed , Karaca Serkan , Ulusoy Hasan Basri , Cam Mustafa , Hokelek Murat , Kuk Salih 
Published: January 2023

Abstract
Leishmaniasis is a neglected tropical disease caused by obligate intracellular protozoan Leishmania parasites. Especially cutaneous form of leishmaniasis has an increasing importance in Turkey because of immigration.
The aims of this study that is supported by the Scientific and Technological Research Council of Turkey (TUBITAK project number 213S149) are to produce Leishmania infantum and L.tropica activated C kinase receptor (LACK) gene based DNA and protein vaccines and to investigate the effectiveness of these vaccines by prime-boost method alone and combined with two adjuvants in-vivo on mice model.
Methodological steps in this study are to culture L.infantum and L.tropica promastigotes in NNN medium, total genomic DNA isolation from culture, cloning activated C kinase receptor (LACK) gene with specific primers, ligation of PCR product into plasmid, amplifying recombinant plasmid in competent cells, producing endotoxin free DNA vaccine, producing endotoxin free LACK recombinant protein, combining DNA and protein vaccines with MPL-SE and CpG-ODN adjuvants and to investigate the effectiveness of this vaccines in-vivo on mice model.
As a result L.infantum and L.tropica LACK gene based DNA and protein vaccines was produced and ready to immunization.
Th-1 and Th-2 immunologic responses are going to be investigated after two week intervals three time vaccination against L.tropica and L.infantum infections on BALB/c mice.
NKp46 expression identifies canine CD3 negative lymphocytes as natural killer cells with phenotypic and functional similarity to those in humans.
Authors: Foltz Jennifer A , Somanchi Srinivas S , Bishop Erin E , Yang Yanwen , Lee Dean A 
Published: January 2023

Abstract
Canines are a unique model to study adoptive immunotherapy for cancer as they spontaneously develop many cancers with homology to human disease. However canine natural killer (NK) cells are poorly defined, rendering the model less useful for study of innate immune responses. NKp46 (NCR1) is an activating receptor expressed on NK cells and is considered a species-wide marker for NK cells, but its’ expression profile has not been demonstrated in canine. Therefore, we set out to determine whether NKp46 defines canine NK cells phenotypically and functionally. To this end, we generated a monoclonal mouse anti-canine NKp46 antibody by immunizing mice with L-cells expressing a canine NKp46 fusion protein. Canine peripheral blood cells were cultured in vitro with feeder cells expressing membrane bound human IL-21. The resultant cells were assessed for expression of NKp46, T-cell, B-cell, and macrophage markers. Expression of other NK cell genes were analyzed by RT-PCR. Cytotoxicity assays were conducted using a calcein-release assay with cancer cell lines. NKp46 is expressed on CD3− primary and cultured cells. Cultured CD3−/NKp46+ canine lymphocytes displayed spontaneous cytotoxicity against canine tumors and expressed NK cell activating receptors. CD3−/NKp46− (null) cultured cells were evident and had intermediate cytotoxicity between CD3+ and CD3−/NKp46+ cells. NKp46 MFI was inducible in these null cells following activation. We are currently investigating the cytokine, chemokine, and transcription factor profiling of CD3−/NKp46+ cells. We conclude that canine CD3−/NKp46+ cells are NK cells with phenotypic and functional similarity to human NK cells. In addition, canines have peripheral blood NK cell precursors that lack NKp46.
Antibody passive immunization against veterinary infectious disease
Authors: Levings Randall 
Published: January 2023

Abstract
The administration of antibodies for passive immunization against infectious agents has recently received increased attention due its use in human treatment for high consequence diseases (e.g., Ebola). The desire for alternatives to antimicrobial pharmaceutical use in food and companion animals has also sparked interest in this product category for veterinary species. Newtechnologies applied to veterinary passive immunization include host-species origin, chimeric, and ‘veticized’ monoclonal antibodies, as well as plantibodies. However, historic husbandry and veterinary practices, and the availability/low cost of food animal (by-)products, have resulted in continued extensive use of more conventional technologies. Injectable polyclonal serum and immunoglobulin specific for viruses, bacteria and toxins are commercially available. Oral colostrum and related products to treat failure of passive transfer in newborns are used in multiple species. Heterologous-species oral antibodies (including chicken IgY for mammalian use) for prevention of enteric disease is yet another category of product. The wide variety of immunoglobulin sources, species immunized, explicit or implied claims, regulations, and human health impacts for this category of materials provide opportunities for expansion and practical use of comparative immunology information.
Development and characterization of monoclonal antibodies specific for chicken IL-8
Authors: Kim Woohyun , Lillehoj Hyun S , Jeong Misun , Min Wongi , Sullivan Yvonne B , Kakach Laura , LaBresh Joanna W 
Published: January 2023

Abstract
Interleukin-8/CXCL8 (IL-8) is a CXC-family chemokine produced by fibroblasts and other cell types, including epithelial cells, endothelial cells, neutrophils, and macrophages. Given that IL-8 attracts lymphocytes to sites of tissue damage, it plays a role in the inflammatory response and wound healing. Chicken chemotactic and angiogenic factor, encoded by the 9E3/CEF4 gene, was identified and has been studied as a human IL-8 homologue for over than 20 years. However, detecting and quantifying of bioactive chemokine/cytokine in avian species is limited by the lack of specific antibodies and reliable bioassays although the use of mAbs has become routine in the mammalian research and diagnosis. Thus, we develop and characterize mouse mAbs against chIL-8 to further define its immunological and biological properties. Two mouse mAbs against chIL-8 were generated using recombinant chIL-8 protein produced in Escherichia coli. These were confirmed to display specific binding with not only recombinants, but also native chIL-8 by Western blot analysis, enzyme-linked immunosorbent assay, and immunocytochemistry. Inhibition of IL-8-induced chemotaxis of peripheral blood lymphocytes, proliferation of chicken macrophage cells and expression of alpha smooth-muscle actin in chicken embryonic fibroblast cells by both antibodies indicate that both antibodies are capable of blocking chIL-8 bioactivity and will be useful reagents for future investigations of inflammation in poultry.
Efficacy of H5 subunit vaccines to protect poultry against highly pathogenic North American H5N2 avian influenza virus
Authors: Sylte Matthew Jon , Torchetti Mia K. , Killian Mary L. , Spackman Erica , Pantin-Jackwood Mary J. , Kapczynski Darrell R. , Suarez David L. , Swayne David E. 
Published: January 2023

Abstract
Between December 2014 and June 2015, North America experienced the H5 highly pathogenic avian influenza (HPAI) epizootic, the largest recorded animal disease outbreak to date where over 48 million commercial poultry (e.g., chickens and turkeys) were euthanized or died from viral exposure. Soon after the epizootic began, the U.S. Department of Agriculture began testing the efficacy of different vaccines as a possible future control strategy. It was unknown whether heterologous H5 vaccines would affect infection and shedding of HPAI H5 virus in experimentally infected commercial chickens and turkeys. Three vaccine technologies were evaluated for efficacy: 1) inactivated reverse genetic laboratory-generated low pathogenicity avian influenza (LPAI) H5 virus encoding H5 hemagglutinin (HA) gene (rgH5), 2) recombinant turkey herpes virus encoding H5 HA (rHVT-H5), and 3) recombinant replication-deficient alphavirus RNA particle vaccine encoding H5 HA (RP-H5). Among all experiments, the rgH5 vaccine (clade 2.3.4.4) gave the best results in preventing mortality and reducing shedding of the North American clade 2.3.4.4 HPAI H5N2 challenge virus in chickens and turkeys. The rHVT-H5 (Clade 2.2) and RP-H5 (clade 2.3.4.4) were most efficacious as a priming vaccine, followed by booster vaccinations with rgH5-inactivated or RP-H5. Heterologous prime (rHVT-H5) and boosting (RP-H5) provided 100% protection in turkeys challenged with HPAI H5N2, whereas a single dose of RP-H5 provided partial protection. Results of these studies led to the conditional approval for RP-H5 vaccine use in poultry as a control measure for future H5 HPAI outbreaks.
Antagonism of MAVS Signaling by Rotavirus Infection
Authors: Ding Siyuan , Greenberg Harry B. 
Published: January 2023

Abstract
The single most important cause of severe gastroenteritis and diarrhea in young children, rotaviruses (RVs) are responsible for an annual 450,000 deaths worldwide. Despite the availability of several vaccines, RV global mortality is still high and significantly less effective in the poorest countries where the burden of disease is greatest. Therefore, there remains an urgent need for a deeper understanding of the basic mechanisms of RV pathogenesis and host-pathogen interaction to develop improved vaccines and novel antiviral therapeutics. The host protein MAVS plays a pivotal role in restricting the replication of many RNA viruses by relaying antiviral signaling from the cytoplasmic RNA sensors RIG-I and MDA5 to downstream interferon (IFN) induction. Multiple virus-encoded factors, including HCV NS3/4A, antagonize the antiviral activity of MAVS by proteolytic cleavage. We recently observed that RV infection specifically mediates the degradation of full-length MAVS but not the truncated variant mini-MAVS. This process is independent of well-characterized IFN antagonist RV NSP1. Given the importance of IFN in suppressing the replication of certain RV strains in vivo, we hypothesize that RVs utilize one or more viral proteins to dampen IFN responses by targeting MAVS signaling. We will mechanistically determine the viral and host factors responsible for MAVS degradation and examine whether it takes place in intestinal epithelial cells in vivo. The current study will broaden our knowledge of RV pathogenesis and provide a molecular basis for the rational design of a new-generation of attenuated RV vaccines.