Annotated lowest variance abstracts citing {'original': '[Ii]mmunother'}

18520304

Immunotherapy for lung cancer.
Penelope A Bradbury, Frances A Shepherd
(Department of Hematology and Oncology, University Health Network, Princess Margaret Hospital, and University of Toronto, Toronto, Ontario, Canada.)
J Thorac Oncol

reports of tumor regression after infection date back as far as bc in the twentieth_century dr william coley witnessing regression of malignant tumor in one of his patients after bacterial_infection developed the first cancer treatment vaccine derived_from killed bacteria with some reported success however despite decades of research no specific active tumor vaccine has_been approved for the treatment of cancer in lung cancer initial attempts to modulate the immune_system with nonspecific therapies were unsuccessful however more_sophisticated specific vaccines have now been developed and an increasing_number are being_evaluated in randomized_phase trials raising hopes that vaccines may_be an additional novel therapy for patients with lung cancer this_article reviews the following seven vaccines which have entered randomized_trials l-blp25 stimuvax bec-2 1e10 pf-3512676 promune melanoma-associated_antigen a3 immunotherapeutic granulocyte-macrophage_colony-stimulating factor-transduced allogeneic cancer cellular immunotherapy and belagenpumatucel-l lucanix

22735380

Immunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12.
José I Quetglas, Juan Dubrot, Jaione Bezunartea, Miguel F Sanmamed, Sandra Hervas-Stubbs, Cristian Smerdou, Ignacio Melero
(Division of Hepatology and Gene Therapy, Center for Applied Medical Research, University of Navarra, Navarra, Spain.)
Mol. Ther.

intratumoral_injection of semliki_forest virus encoding interleukin-12 sfv-il-12 combines acute expression of il-12 and stressful apoptosis of infected malignant cells agonist antibodies_directed to costimulatory receptor cd137 4-1bb strongly amplify pre-existing cellular immune_responses toward weak tumor antigens in this_study we provide_evidence for powerful synergistic_effects of combined strategy consisting of intratumoral_injection of sfv-il-12 and systemic_delivery of agonist anti-cd137 monoclonal_antibodies mabs which was substantiated against poorly_immunogenic b16 melanomas b16-ova and b16_f10 and tc-1 lung carcinomas effector cd8_cells were sufficient to mediate complete tumor eradications accordingly there was an intensely synergistic in vivo enhancement of cytotoxic_lymphocytes ctl mediated immunity_against the tumor antigens ova and tyrosine-related protein-2 trp-2 this train of phenomena led to long-lasting tumor-specific_immunity against rechallenge attained transient control of the progression of concomitant tumor lesions that were not directly treated with sfv-il-12 and caused autoimmune vitiligo importantly we found that sfv-il-12 intratumoral_injection induces bright expression of cd137 on most tumor-infiltrating cd8_lymphocytes thereby_providing more abundant targets for the action of the agonist antibody this efficacious combinatorial immunotherapy strategy offers feasibility for clinical translation since anti-cd137 mabs are already undergoing clinical_trials and development of clinical-grade sfv-il-12 vectors is in progress

16001959

Dendritic cell-derived exosomes in cancer immunotherapy: exploiting nature's antigen delivery pathway.
Alain Delcayre, Helen Shu, Jean-Bernard Le Pecq
(Anosys Inc., 1014 Hamilton Court, Menlo Park, CA 94025, USA. adelcayre@anosys.com)
Expert Rev Anticancer Ther

dendritic_cells release large_quantities of exosomes known as dexosomes these dexosomes are heat-stable small vesicles 60-90 nm in diameter made_up of lipid_bilayer displaying an enrichment in sphingomyelin and decrease in phosphatidylcholine content with no measurable asymmetry they incorporate characteristic set of proteins including large quantity of tetraspanins such_as cd9 and cd81 all the known antigen_presenting molecules major_histocompatibility complex_class and ii cd1 and and the costimulatory_molecule cd86 the function of dexosomes is to transfer antigen-loaded major_histocompatibility complex_class and ii molecules and other associated molecules to naive dendritic_cells potentially leading to the amplification of the cellular immune_response in preclinical mouse_models antigen-loaded dexosomes elicit strong_antitumor activity human dexosomes can_be prepared ex_vivo relatively easily from dendritic_cells derived_from monocytes isolated by leukapheresis of healthy_individuals or cancer patients the feasibility of using dexosomes as cancer therapeutic vaccine has_been tested in two phase clinical studies in melanoma and lung cancer patients respectively these studies demonstrate_that dexosomes can_be prepared_from cancer patient blood cells and be_safely administered clinical observations suggested_that dexosomes can stimulate both the adaptive t-cells and innate natural_killer cells cellular immune_responses this_review focuses_on the perspective of using dexosomes in cancer immunotherapy concepts for using the exosome pathway in other possible pharmacologic applications are also discussed

10803326

Apparent pokeweed mitogen cure of metastatic gum melanoma in an older dog.
B M Wimer, P L Mann
(JBMW Immunotherapeutics, Albuquerque, NM 87123-4255, USA.)
Cancer Biother. Radiopharm.

immunotherapy with plant mitogens has_been of increasing_interest to both authors although their_mutual attraction to these substances over the past two_decades occurred independently and has taken divergent pathways from the start because of their clinical unavailability wimer efforts have_been confined to writing theoretical concepts on potential applications of the mitogens focusing_on the l4 isolectin of pha alternatively mann has worked actively with laboratory and experimental research involving pwm that he has extracted himself as sequel to pilot_study of pwm cancer treatment in pets whereby he supplies the mitogen protocol and data sheets and veterinarians supervise the administration mann acquiesced to widespread requests for inclusion in an extended investigation unfortunately this arrangement has left mann with little control over data submission and until_recently only verbal reports have_been received the recent documentation of three-year remission and apparent cure of gum melanoma metastatic to regional and hilar_lymph nodes and to the lungs in an aged dog following pwm therapy has_prompted this case_report the incredible response has inspired more_aggressive attempts to obtain_information from other recipients of the mitogen the small total_dose of micrograms inducing remission does speak for the remarkable potency of pwm that may_be or more times that of pha however the possibility that melanoma is uniquely responsive tumor is suggested by article indicating complete_remission of metastatic melanoma in an_18-year-old lad to an unexpectedly low total_dose of mg pha preliminary reports on other tumors treated with pwm indicate some impressive responses have occurred although they also suggest_that mann regimen may sometimes require adjustments in dosages and other variables previously reviewed in theoretical pha-l4 models to which this case_report now contributes validity

15899830

Immune selection and emergence of aggressive tumor variants as negative consequences of Fas-mediated cytotoxicity and altered IFN-gamma-regulated gene expression.
Kebin Liu, Sheila A Caldwell, Scott I Abrams
(Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892-1402, USA.)
Cancer Res.

antitumor_responses can_be induced in patients via active or adoptive_immunotherapy yet complete tumor eradication occurs_infrequently this paradox in tumor immunology led_us to address two questions does an antitumor response which is intended to destroy the aberrant target population also at the same_time select for aggressive tumor variants atv in vivo? if this process does occur what is the contribution of the perforin or fas-mediated effector mechanism in the immune selection of such atv? here in an experimental mouse lung metastasis model we showed that atv generated either naturally in vivo or in vitro by anti-fas selection resembled each other biologically and genetically as judged by enhanced tumor growth and genome-scale gene expression_profiling respectively furthermore atv that survived ctl adoptive_immunotherapy displayed an even more profound loss of fas expression and function as_well as enhanced malignant proficiency in vivo atv however retained sensitivity to perforin-mediated lysis in vitro lastly such atv displayed diminished responsiveness in their expression of ifn-gamma-regulated genes including those mechanistically linked to fas-mediated death fas and caspase-1 overall we showed that immune selection did occur in vivo and played an_important role in the emergence of atv atv bearing fas-resistant phenotype was chief consequence of immune selection and an overall diminished responsiveness of ifn-gamma-regulated gene expression was characteristic of atv thus in this model fas-mediated cytotoxicity in concert with ifn-gamma-regulated gene expression mechanistically constituted significant determinants of immune selection of atv in vivo

23529308

Foxp3 and IL17 expression in tumor infiltrating lymphocytes (TIL) and tumor cells - correlated or independent factors?
Florina Vasilescu, D Arsene, Florina Cionca, Maria Comănescu, V Enache, Cristina Iosif, D O Alexandru, D Georgescu, Camelia Dobrea, Adina Bălan, Carmen Ardeleanu
(Department of Pathology, "Victor Babes" National Institute of Pathology, Bucharest, Romania.)
Rom J Morphol Embryol

tumor infiltrating_lymphocytes til as microenvironment component were studied in various epithelial tumors with contradictory_results recent data about regulatory_t-cells treg revealed new explanations for pro and anti-tumor implications of til tregs immunoprofile was recently_completed with foxp3 expression t-cell fraction th is producing cytokine il17 and is now considered acting in tumor progression our study_aimed to analyze immunohistochemically ihc foxp3+ and il17 expression in resected lung adenocarcinomas since they could become possible targets in the antitumor immunotherapy the studied material was represented by paraffin-embedded tumor fragments from patients with til identified on he staining the antibodies used were foxp3 and il17 the statistical_analysis used logistical regression on spss19 software chicago il usa til was usually mild or scarce positive statistic correlation resulted between the amounts of til in peritumoral and intratumoral location but without correlation to histopathological grading foxp3 and il17 were present in til lymphocytes tumor cells and fibroblasts il17 was expressed also in periendothelial cells pec foxp3 positivity was significantly_correlated for lymphocytes÷tumor cells lymphocytes÷fibroblasts and tumor cells÷fibroblasts suggesting their concerted_action tumor cells and lymphocytes foxp3 expression was inversely_correlated with the amount of til between lymphocytic foxp3 and pec il17 we found weak negative_correlation the til had quite positive_correlation with pec il17 in these conditions foxp3 could_be mediator of the tumor cells inhibitory aggression upon the immune_system and could_be used as molecular target for biological antitumor therapy

20406989

4-1BB ligand as an effective multifunctional immunomodulator and antigen delivery vehicle for the development of therapeutic cancer vaccines.
Rajesh K Sharma, Rich-Henry Schabowsky, Abhishek K Srivastava, Kutlu G Elpek, Shravan Madireddi, Hong Zhao, Zhenping Zhong, Robert W Miller, Kathryn J Macleod, Esma S Yolcu, Haval Shirwan
(Department of Microbiology and Immunology, James Brown Cancer Center, Institute for Cellular Therapeutics, University of Louisville and ApoImmune, Inc, Louisville, Kentucky, USA.)
Cancer Res.

therapeutic subunit vaccines based_on tumor-associated_antigens taa represent an_attractive approach for the treatment of cancer however poor immunogenicity of taas requires potent adjuvants for therapeutic_efficacy we recently_proposed the tumor_necrosis factor family costimulatory ligands as potential adjuvants for therapeutic vaccines and hence generated soluble_form of 4-1bbl chimeric with streptavidin sa-4-1bbl that has pleiotropic_effects on cells of innate adaptive and regulatory immunity we herein tested whether these effects can translate_into effective cancer immunotherapy when sa-4-1bbl was also used as vehicle to deliver taas in vivo to dendritic_cells dcs constitutively_expressing the 4-1bb receptor sa-4-1bbl was internalized by dcs upon receptor binding and immunization with biotinylated antigens conjugated to sa-4-1bbl resulted in increased antigen uptake and cross-presentation by dcs leading to the generation of effective t-cell immune_responses conjugate vaccines containing human_papillomavirus e7_oncoprotein or survivin as self-taa had potent therapeutic_efficacy against tc-1 cervical and 3ll lung carcinoma tumors respectively therapeutic_efficacy of the vaccines was associated_with increased cd4 and cd8_t-cell effector and memory responses and higher intratumoral cd8 effector/cd4 cd25_foxp3 regulatory cell ratio thus potent pleiotropic immune functions of sa-4-1bbl combined with its_ability to serve_as vehicle to increase the delivery of antigens to dcs in vivo endow this molecule with the potential to serve_as an effective immunomodulatory component of therapeutic vaccines against cancer and chronic infections

22174445

Identification of innate IL-5-producing cells and their role in lung eosinophil regulation and antitumor immunity.
Masashi Ikutani, Tsutomu Yanagibashi, Masaru Ogasawara, Koichi Tsuneyama, Seiji Yamamoto, Yuichi Hattori, Taku Kouro, Atsuko Itakura, Yoshinori Nagai, Satoshi Takaki, Kiyoshi Takatsu
(Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama 930-0194, Japan.)
J. Immunol.

il-5 is involved in number of immune_responses such_as helminth infection and allergy il-5 also plays roles in innate_immunity by maintaining b-1 cells and mucosal iga production however the identity of il-5-producing cells has not been unambiguously characterized in this report we_describe the generation of an il-5 reporter mouse and identify il-5-producing non-t lymphoid cells that reside in the intestine peritoneal_cavity and lungs in naive_mice they_share many characteristics with natural helper cells nuocytes and ih2 cells including surface ags and responsiveness to cytokines however these phenotypes do_not completely overlap with any particular one of these cell types innate non-t il-5-producing cells localized most abundantly in the lung and proliferated and upregulated il-5 production in response to il-25 and il-33 il-33 was more_effective than il-25 these cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated_by il-25 and il-33 given that eosinophils are shown to possess antitumor_activity we studied lung tumor metastasis and showed that innate il-5-producing cells were increased in response to tumor invasion and their regulation of eosinophils is critical to suppress tumor metastasis genetic blockade or neutralization of il-5 impaired eosinophil recruitment into the lung and resulted in increased tumor metastasis conversely exogenous il-5 treatment resulted in suppressed tumor metastasis and augmented eosinophil infiltration these newly_identified innate il-5-producing cells thus play_role in tumor surveillance through lung eosinophils and may_contribute to development of novel immunotherapies for cancer

24450537

Immunotherapy for malignant pleural mesothelioma. Current status and future prospects.
Raymond M Wong, Irina Ianculescu, Sherven Sharma, Diana L Gage, Olga M Olevsky, Svetlana Kotova, Marko N Kostic, Warren S Grundfest, Dongmei Hou, Robert B Cameron
(1 Pacific Meso Center at the Pacific Heart, Lung & Blood Institute, Los Angeles, California.)
Am. J. Respir. Cell Mol. Biol.

malignant_pleural mesothelioma_mpm is rare malignancy of the pleura that is frequently resistant to conventional_therapies immunotherapy is promising investigational approach for mpm that has shown some evidence of clinical_benefit in select patients however tumor-induced_immunosuppression is likely major_impediment to achieving optimal clinical responses to immunotherapeutic intervention mpm contains variable_degree of infiltrating t-regulatory_cells and m2_macrophages which are believed to facilitate tumor evasion from the host_immune system additional immunosuppressive factors identified in other human tumor types such_as tumor-associated programmed death ligand-1 expression may_be relevant for investigation in mpm conventional cytoreductive therapies such_as radiation chemotherapy and surgery may_play critical_role in successful immunotherapeutic_strategies by ablating intratumoral and/or systemic immunosuppressive factors thus creating host_environment more amenable to immunotherapy this_article reviews the immunotherapeutic_approaches being_evaluated in patients with mpm and discusses_how immunotherapy might_be rationally combined with conventional tumor cytoreductive therapies for this disease

23831323

Flagellin enhances tumor-specific CD8⁺ T cell immune responses through TLR5 stimulation in a therapeutic cancer vaccine model.
Chung Truong Nguyen, Seol Hee Hong, Jeong-Im Sin, Hong Van Dinh Vu, Kwangjoon Jeong, Kyoung Oh Cho, Satoshi Uematsu, Shizuo Akira, Shee Eun Lee, Joon Haeng Rhee
(Clinical Vaccine R&D Center, Chonnam National University, Gwangju 500-757, Republic of Korea.)
Vaccine

tumor antigen ta specific immunotherapy is an emerging approach for cancer treatment potent adjuvants are prerequisites to the immunotherapy for overcoming the low immunogenicity of tas we previously demonstrated that bacterial flagellin vibrio vulnificus flab has potent adjuvant activity in various vaccination models in this_study we_investigated whether the flab protein could_be potent adjuvant for human_papillomavirus e6 and e7 e6/e7 peptide-based anticancer immunotherapy we used an e6/e7-expressing tc-1 carcinoma implantation animal_model and tested ta-specific immunomodulation by flab we co-administered the e6/e7 peptide either with or without flab into tc-1 tumor-bearing_mice and then analyzed the antitumor_activity of the peptide flab significantly potentiated specific antitumor_immune responses_elicited by the peptide immunization as_evidenced by retarded in vivo tumor growth and significantly_prolonged survival we noticed that tc-1 cells do_not express toll-like_receptor tlr5 on their surface and the tlr5 signaling_pathway in tc-1 cells was not responsible_for the antitumor_effect of flab flab potentiated the ctl_activity and ag-specific ifn-γ_production of cd8_cells from the draining_lymph node and spleen in addition this antitumor_activity was abrogated following the in vivo depletion of cd8_cells and in tlr5 knockout_ko or myd88 ko_mice these_results suggest_that flagellin could_enhance ta-specific cd8_ctl immune_responses through tlr5 stimulation in cancer immunotherapy