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Subcutaneous immunotherapy

Stacey Bagby, Wells A Messersmith, Todd M Pitts, Anna Capasso, Marileila Varella-Garcia, Peter J Klauck, Jihye Kim, Aik-Choon Tan, S Gail Eckhardt, John J Tentler, John Arcaroli
Patient derived tumor xenograft (PDTX) models provide a necessary platform in facilitating anti-cancer drug development prior to human trials. Human tumor pieces are injected subcutaneously into athymic nude mice (immunocompromised, T cell deficient) to create a bank of tumors and subsequently are passaged into different generations of mice in order to maintain these tumors from patients. Importantly, cellular heterogeneity of the original tumor is closely emulated in this model, which provides a more clinically relevant model for evaluation of drug efficacy studies (single agent and combination), biomarker analysis, resistant pathways and cancer stem cell biology...
September 30, 2016: Journal of Visualized Experiments: JoVE
Pravin Kesarwani, Paramita Chakraborty, Radhika Gudi, Shilpak Chatterjee, Gina Scurti, Kyle Toth, Patt Simms, Mahvash Husain, Kent Armeson, Shahid Husain, Elizabeth Garrett-Mayer, Chethamarakshan Vasu, Michael I Nishimura, Shikhar Mehrotra
Advancements in adoptive cell transfer therapy (ACT) has led to the use of T cells engineered with tumor specific T cell receptors, which after rapid expansion can be obtained in sufficient numbers for treating patients. However, due to massive proliferation these cells are close to replicative senescence, exhibit exhausted phenotype, and also display increased susceptibility to activation induced cell death. We have previously shown that tumor reactive T cells undergo caspase-independent cell death upon TCR restimulation with cognate antigen, which involves reactive oxygen species and c-jun N-terminal kinase...
October 14, 2016: Oncotarget
Yi-An Zhang, Hai-Ning Liu, Ji-Min Zhu, Dan-Ying Zhang, Xi-Zhong Shen, Tao-Tao Liu
BACKGROUND: The mechanism of Nova1's role in hepatocellular carcinoma has not been delineated. Also its interaction with GABAA receptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABAARγ2 in human hepatocellular carcinoma. And its role in HCC tumorigenesis under the regulation of its alternative splicing factor Nova1. METHODS: Immunohistochemistry staining was used to investigate the distribution and clinical significance of GABAARγ2 protein expression in hepatocellular carcinoma...
October 12, 2016: Journal of Biomedical Science
John A Todd, Marina Evangelou, Antony J Cutler, Marcin L Pekalski, Neil M Walker, Helen E Stevens, Linsey Porter, Deborah J Smyth, Daniel B Rainbow, Ricardo C Ferreira, Laura Esposito, Kara M D Hunter, Kevin Loudon, Kathryn Irons, Jennie H Yang, Charles J M Bell, Helen Schuilenburg, James Heywood, Ben Challis, Sankalpa Neupane, Pamela Clarke, Gillian Coleman, Sarah Dawson, Donna Goymer, Katerina Anselmiova, Jane Kennet, Judy Brown, Sarah L Caddy, Jia Lu, Jane Greatorex, Ian Goodfellow, Chris Wallace, Tim I Tree, Mark Evans, Adrian P Mander, Simon Bond, Linda S Wicker, Frank Waldron-Lynch
BACKGROUND: Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs...
October 2016: PLoS Medicine
Manglio Rizzo, Laura Alaniz, Guillermo D Mazzolini
In recent years immunotherapy has revolutionized the treatment of patients with advanced cancer. The increased knowledge in the tumor immune-biology has allowed developing rational treatments by manipulation of the immune system with significant clinical impact. This rapid development has significantly changed the prognosis of many tumors without treatment options up to date. Other strategies have explored the use of therapeutic vaccines based on dendritic cells (DC) by inducing antitumor immunity. DC are cells of hematopoietic origin, constitutively expressing molecules capable to present antigens, that are functionally the most potent inducers of the activation and proliferation of antigen specific T lymphocytes...
2016: Medicina
Anning Li, Yue Wu, Jenny Linnoila, Benjamin Pulli, Cuihua Wang, Matthias Zeller, Muhammad Ali, Grant K Lewandrowski, Jinghui Li, Benoit Tricot, Edmund Keliher, Gregory R Wojtkiewicz, Giulia Fulci, Xiaoyuan Feng, Bakhos A Tannous, Zhenwei Yao, John W Chen
Currently, there is no stable and flexible method to label and track cytotoxic T lymphocytes (CTLs) in vivo in CTL immunotherapy. We aimed to evaluate whether the sulfo-hydroxysuccinimide (NHS)-biotin-streptavidin (SA) platform could chemically modify the cell surface of CTLs for in vivo tracking. CD8+ T lymphocytes were labeled with sulfo-NHS-biotin under different conditions and then incubated with SA-Alexa647. Labeling efficiency was proportional to sulfo-NHS-biotin concentration. CD8+ T lymphocytes could be labeled with higher efficiency with sulfo-NHS-biotin in DPBS than in RPMI (P < 0...
October 8, 2016: Cancer Immunology, Immunotherapy: CII
Moisés A Calderón, Carmen Vidal, Pablo Rodríguez Del Río, Jocelyne Just, Oliver Pfaar, Ana I Tabar, Inmaculada Sánchez-Machín, Petra Bubel, Jesus Borja, Peter Eberle, Rainer Reiber, Michel Bouvier, Alain Lepelliez, Ludger Klimek, Pascal Demoly
BACKGROUND: Outside clinical trials, data on systemic reactions (SRs) due to allergen immunotherapy (AIT) are scarce. METHODS: A prospective, longitudinal, web-based survey of "real-life" respiratory allergen immunotherapy (AIT) clinical practice was conducted in France, Germany and Spain. SRs were recorded and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and risk factors associated with SRs were identified. RESULTS: A total of 4,316 patients (corresponding to 4,363 ongoing courses of AIT) were included...
October 8, 2016: Allergy
Li Ding, Yuan Meng, Hui-Yi Zhang, Wen-Chao Yin, Yi Yan, Yun-Peng Cao
Active amyloid-β (Aβ) immunotherapy is effective in preventing Aβ deposition, facilitating plaque clearance, and improving cognitive functions in mouse models of Alzheimer's disease (AD). Developing a safe and effective AD vaccine requires a delicate balance between inducing adequate humoral immune responses and avoiding T cell-mediated autoimmune responses. In this study, we designed 2 peptide epitope vaccines, Aβ3-10-KLH and 5Aβ3-10, prepared respectively by coupling Aβ3-10 to the immunogenic carrier protein keyhole limpet hemocyanin (KLH) or by joining 5 Aβ3-10 epitopes linearly in tandem...
September 28, 2016: Neuroscience Letters
Xiao X Wei, Stephen Chan, Serena Kwek, Jera Lewis, Vinh Dao, Li Zhang, Matthew R Cooperberg, Charles J Ryan, Amy M Lin, Terence W Friedlander, Brian Rini, Christopher Kane, Jeffry P Simko, Peter R Carroll, Eric J Small, Lawrence Fong
Granulocytic-macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients with localized prostate cancer undergoing radical prostatectomy. Patients received subcutaneous injections of GM-CSF (250 μg/m(2)/day) daily for 2 weeks (cohort 1; n = 6), 3 weeks (cohort 2; n = 6), or 4 weeks (cohort 3; n = 6)...
September 29, 2016: Cancer Immunology Research
Joseph G Pressey, Julia Adams, Lualhati Harkins, David Kelly, Zhiying You, Lawrence S Lamb
INTRODUCTION: CD3+ γδ+ T cells comprise 2% to 5% of circulating T cells with Vγ9Vδ2+ cells the dominant circulating subtype. Vγ9Vδ2+ cells recognize non-peptide phosphoantigens and stress-associated NKG2D ligands expressed on malignant cells. Strategies that incorporate the tumoricidal properties of γδ T cells represent a promising immunotherapeutic strategy for treatment of solid malignancies including neuroblastoma (NB). In this prospective, non-randomized Phase I trial, we assessed whether circulating Vγ9Vδ2+ cells could be safely expanded using intravenous ZOL (Zoledronate [Zometa]) and subcutaneous Interleukin-2 (IL-2) in patients with refractory NB...
September 2016: Medicine (Baltimore)
Saeid Zanganeh, Gregor Hutter, Ryan Spitler, Olga Lenkov, Morteza Mahmoudi, Aubie Shaw, Jukka Sakari Pajarinen, Hossein Nejadnik, Stuart Goodman, Michael Moseley, Lisa Marie Coussens, Heike Elisabeth Daldrup-Link
Until now, the Food and Drug Administration (FDA)-approved iron supplement ferumoxytol and other iron oxide nanoparticles have been used for treating iron deficiency, as contrast agents for magnetic resonance imaging and as drug carriers. Here, we show an intrinsic therapeutic effect of ferumoxytol on the growth of early mammary cancers, and lung cancer metastases in liver and lungs. In vitro, adenocarcinoma cells co-incubated with ferumoxytol and macrophages showed increased caspase-3 activity. Macrophages exposed to ferumoxytol displayed increased mRNA associated with pro-inflammatory Th1-type responses...
September 26, 2016: Nature Nanotechnology
Halie M Anderson, Robert A Wood, William W Busse
Allergic rhinitis (AR) is a common illness in children and can impair their quality of life. Furthermore, many children remain symptomatic despite maximizing systemic antihistamine and topical therapies. It is at this clinical juncture that immunotherapy may be considered. The efficacy and safety associated with both subcutaneous (SCIT) and sublingual (SLIT) approaches are reviewed and positioned as treatment options for pediatric patients, with specific focus on current literature as it relates to SLIT in children, including those with perennial allergic rhinitis...
September 21, 2016: Journal of Allergy and Clinical Immunology in Practice
Yan Li, Kyosuke Kobayashi, Marwa M Mona, Chikako Satomi, Shinji Okano, Hiroyuki Inoue, Kenzaburo Tani, Atsushi Takahashi
BACKGROUND: FEAT is an intracellular protein that potently drives tumorigenesis in vivo. It is only weakly expressed in normal human tissues, including the testis. In contrast, FEAT is aberrantly upregulated in most human cancers. The present study was designed to investigate whether FEAT is applicable to tumor immunotherapy and whether FEAT is discernible in the bloodstream as a molecular biomarker of human cancers. METHODS: Two mouse FEAT peptides with predicted affinities for major histocompatibility complex H-2Kb and H-2Db were injected subcutaneously into C57BL/6 mice before subcutaneous transplantation of isogenic B16-F10 melanoma cells...
2016: Journal of Translational Medicine
Petra Zieglmayer, Margarete Focke-Tejkl, René Schmutz, Patrick Lemell, René Zieglmayer, Milena Weber, Renata Kiss, Katharina Blatt, Peter Valent, Frank Stolz, Hans Huber, Angela Neubauer, Anette Knoll, Friedrich Horak, Rainer Henning, Rudolf Valenta
BACKGROUND: We have developed a recombinant B cell epitope-based vaccine (BM32) for allergen-specific immunotherapy (AIT) of grass pollen allergy. The vaccine contains recombinant fusion proteins consisting of allergen-derived peptides and the hepatitis B surface protein domain preS as immunological carrier. METHODS: We conducted a randomized, double-blind, placebo-controlled AIT study to determine safety, clinical efficacy and immunological mechanism of three subcutaneous injections of three BM32 doses adsorbed to aluminum hydroxide versus aluminum hydroxide (placebo) applied monthly to grass pollen allergic patients (n=70)...
September 2016: EBioMedicine
Mohanraj Ramachandran, Di Yu, Matheus Dyczynski, Sathishkumar Baskaran, Lei Zhang, Sirle Saul, Aleksei Lulla, Valeria Lulla, Sven Nelander, Anna Dimberg, Andres Merits, Justyna Leja-Jarblad, Magnus Essand
PURPOSE: Glioblastoma multiforme (GBM) and high-risk neuroblastoma are cancers with poor outcome. Immunotherapy in the form of neurotropic oncolytic viruses is a promising therapeutic strategy for these malignancies. Here we evaluate the oncolytic potential of the neurovirulent and partly interferon (IFN)-β-resistant Semliki Forest virus (SFV)-4 in GBMs and neuroblastomas. To reduce neurovirulence we constructed SFV4miRT, which is attenuated in normal CNS cells through insertion of microRNA target sequences for miR124, miR125, miR134 Experimental Design:Oncolytic activity of SFV4miRT was examined in mouse neuroblastoma and GBM cell lines and in patient-derived human glioblastoma cell cultures (HGCC)...
September 16, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Pablo Rodríguez Del Río, Carmen Vidal, Jocelyne Just, Ana I Tabar, Inmaculada Sanchez-Machin, Peter Eberle, Jesus Borja, Petra Bubel, Oliver Pfaar, Pascal Demoly, Moises A Calderón
BACKGROUND: Safety data on "real-life" allergen immunotherapy (AIT) in children and adolescents is usually extrapolated from studies in adults. METHODS: Patients aged 18 or under initiating aeroallergen AIT were evaluated in a prospective European survey. Patient profiles and systemic reactions (SRs) were recorded. Descriptive, univariate and multivariate analyses were used to identify risk factors for SRs. RESULTS: A total of 1,563 patients (mean±SD age: 11...
September 17, 2016: Pediatric Allergy and Immunology
Olga Leplina, Nataliya Starostina, Olga Zheltova, Alexandr Ostanin, Ekaterina Shevela, Elena Chernykh
Recurrent herpes simplex labialis caused predominantly with herpes simplexvirus 1(HSV-1) is a major problem, for which various treatments have minimal impact. Given the important role of the immune system in controlling virus infection, an activation of virus-specific immune responses, in particular,using dendritic cell (DCs) vaccines, seems to be a promising approach for the treatment of patients with frequent recurrences of herpes labialis. The current paper presents the results of a pilot study of the safety and efficacy of DC vaccines in 14 patients with recurrent HSV-1 infections...
July 26, 2016: Human Vaccines & Immunotherapeutics
Kristina Berg Lorvik, Clara Hammarstrom, Marte Fauskanger, Ole Audun Werner Haabeth, Michael Zangani, Guttorm Haraldsen, Bjarne Bogen, Alexandre Corthay
Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8+ T cells, however, the potential of CD4+ T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with interferon-γ (IFNγ)-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with Major Histocompatibility Complex (MHC) class II-negative myeloma...
September 12, 2016: Cancer Research
Masahiro Azuma, Yohei Takeda, Hiroko Nakajima, Haruo Sugiyama, Takashi Ebihara, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Successful cancer immunotherapy necessitates T cell proliferation and infiltration into tumor without exhaustion, a process closely links optimal maturation of dendritic cells (DC), and adjuvant promotes this process as an essential prerequisite. Poly(I:C) has contributed to adjuvant immunotherapy that evokes an antitumor response through the Toll-loke receptor 3 (TLR3)/TICAM-1 pathway in DC. However, the mechanism whereby Poly(I:C) acts on DC for T cell proliferation and migration remains undetermined. Subcutaneous injection of Poly(I:C) regressed implant tumors (WT1-C1498 or OVA-EG7) in C57BL/6 mice, which coincided with tumor-infiltration of CD8(+) T cells...
August 2016: Oncoimmunology
M Rodríguez Mosquera, F J Sola Martínez, A Montoro de Francisco, T Chivato Pérez, V Sánchez Moreno, A Rodríguez-Marco, J Hernández-Peña
This study was designed to determine the level of satisfaction, tolerance and perceived effectiveness by patients in the first pollen season after starting treatment with Alergovit(®). For this purpose, a nationwide, retrospective, multicentre and cross-sectional observational study was carried on 256 patients. Perceived effectiveness by the patients was measured using a visual analogue scale and was clinically significant in 92.4% of the patients. The satisfaction level was evaluated with a specific questionnaire...
September 2016: European Annals of Allergy and Clinical Immunology
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