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

18445513

Perspectives on microbes as oncogenic infectious agents and implications for breast cancer.
Zeena E Nackerdien
(Raymond and Beverly Sackler Laboratory of Molecular Genetics and Informatics, Rockefeller University, 1230 York Ave, New York, NY 10021-6399, USA. nackerz@mail.rockefeller.edu)
Med. Hypotheses

cancer management is partly based_on weighing risk_factors attributed to noninfectious agents human genes and epigenetic factors infectious disease causation has largely been restricted to genes directly responsible_for causing cancer after sustaining damage oncogenes lately evidence has_emerged linking infectious_agents to number of chronic_diseases these studies have recognized the influence that acute atypical latent and chronic infections may_play in tricking the immune_system and affecting disease etiology similar evidence is emerging in model_systems with_respect to the role of infectious_agents in gastrointestinal liver and lung cancers although viruses have_been found in association with breast cancer skepticism remains about role for other infectious_agents notably microbes in the disease etiology improved experimental_designs employed in different cancer studies and less rigid definition of infectious causation may aid in confirming or refuting microbe-breast cancer connection cancer recurrence could_potentially be_minimized and treatment_options further tailored on case by case basis if microbes/microbial components/strain variants associated_with breast cancer are identified probiotics are employed to reduce treatment side-effects and if microbes could effectively be_harnessed in immunotherapy

19254781

Autoimmune thyroiditis as an indicator of autoimmune sequelae during cancer immunotherapy.
Yi-chi M Kong, Jennifer B Jacob, Jeffrey C Flynn, Bruce E Elliott, Wei-Zen Wei
(Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. ykong@med.wayne.edu)
Autoimmun Rev

improving cancer immunotherapy by targeting cell network also triggers autoimmunity we disrupted regulatory cell treg function to probe the balance_between breast cancer vaccination and autoimmune_thyroiditis eat in four models with particular_attention to mhc-associated susceptibility eat induction with mouse thyroglobulin mtg without adjuvant and tolerance to her-2/neu in transgenic_mice in eat-resistant balb/c_mice treg_depletion enhanced tumor regression and facilitated mild thyroiditis induction in her-2 tolerant c57bl/6_mice expressing hla-dr3 an eat-susceptibility allele her-2 dna vaccinations must follow treg_depletion for her-2xdr3 mice to resist tumor challenge thyroiditis incidence was moderated by the eat-resistant ia allele in neu tolerant eat-resistant balb/c_mice implanted neu tumor also regressed only after treg_depletion and dna vaccinations tumor immunity was long-term providing protection from spontaneous tumorigenesis in all three immune stimuli from concurrent tumor regression and eat development have noticeable mutually augmenting effect in treg-depleted eat-susceptible cba/j mice strong tumor protection was established by immunization with cell vaccine mtg injections led to greater thyroiditis incidence and severity combination models with mhc_class ii diversity should facilitate autoimmunity risk assessment and management while generating tumor immunity

22636320

Monocyte-derived dendritic cells from breast cancer patients are biased to induce CD4+CD25+Foxp3+ regulatory T cells.
Rodrigo Nalio Ramos, Lilian Sally Chin, Ana Paula S A Dos Santos, Patrícia Cruz Bergami-Santos, Fábio Laginha, José Alexandre M Barbuto
(Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.)
J. Leukoc. Biol.

dcs orchestrate immune_responses contributing to the pattern of response developed in cancer dcs may_play dysfunctional role in the induction of cd4_cd25 foxp3_tregs contributing to immune_evasion we_show here that mo-dcs from breast cancer patients show an altered phenotype and induce preferentially tregs phenomenon that occurred regardless of dc_maturation stimulus scd40l cytokine cocktail tnf-α and lps the mo-dcs of patients induced low proliferation of allogeneic cd3 cd25 neg foxp3 neg cells which after becoming cd25 suppressed mitogen-stimulated cells contrastingly mo-dcs from healthy_donors induced stronger proliferative response low frequency of cd4_cd25 foxp3 with no suppressive activity furthermore healthy mo-dcs induced higher levels of ifn-γ whereas the mo-dcs of patients induced higher levels of bioactive tgf-β1 and il-10 in cocultures with allogeneic cells interestingly tgf-β1 blocking with mab in cocultures was not enough to completely revert the mo-dcs of patients bias_toward treg induction altogether_these findings should_be considered in immunotherapeutic_approaches for cancer based_on mo-dcs

18633610

Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth.
Markus Loeffler, Gaelle Le'Negrate, Maryla Krajewska, John C Reed
(Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.)
Cancer Immunol. Immunother.

intravenously-applied bacteria tend to accumulate in tumors and can sporadically lead to tumor regression systemic_administration of attenuated_salmonella typhimurium is safe and has shown no_significant adverse_effects in humans the purpose of this_study was to test the hypothesis that engineering typhimurium to express chemokine ccl21 would increase anti-tumor_activity we engineered an attenuated strain of typhimurium to produce the chemokine ccl21 attenuated typhimurium expressing ccl21 significantly_inhibited the growth of primary tumors and pulmonary_metastases in preclinical_models of multi-drug-resistant murine carcinomas while control bacteria did_not histological analysis of tumors showed marked inflammatory cell infiltrates in mice treated with ccl21-expressing but_not control bacteria levels of cytokines and chemokines known to be induced by ccl21 interferon-gamma infgamma cxcl9 and cxcl10 were significantly_elevated in tumors of mice treated with ccl21-expressing but_not control typhimurium the anti-tumor_activity was found to be dependent_on cd4 and cd8-expressing cells based_on antibody-mediated in vivo immuno-depletion experiments anti-tumor_activity was achieved without evidence of toxicity in summary chemokine-expressing attenuated bacteria may provide novel approach to cancer immunotherapy for effective and well-tolerated in vivo delivery of immunomodulatory proteins

21050308

Immunoprevention and immunotherapy of mammary carcinoma.
Pier-Luigi Lollini, Giordano Nicoletti, Lorena Landuzzi, Carla De Giovanni, Patrizia Nanni
(Department of Hematology and Oncological Sciences, University of Bologna, Bologna, Italy. pierluigi.lollini@unibo.it)
Breast J

cancer immunoprevention posits that the enhancement of immune_defenses in healthy_individuals could control tumor onset immunoprevention of viral tumors is already implemented at the population level for human hepatocellular and cervical carcinomas altogether viral vaccines could prevent more_than of all human tumors the big question is whether immunoprevention can_be applied to nonviral tumors including breast cancer promising results were obtained in preclinical_models in particular in her-2/neu transgenic_mice which are prone to mammary carcinoma development using vaccines_against her-2/neu_oncoprotein p185 the life_expectancy of vaccinated mice was more_than doubled protective immune mechanisms elicited by effective vaccines were mainly based_on helper cell cytokines in particular γ-interferon and anti-p185 antibodies the term oncoantigens was coined to define those antigenic molecules that like her-2 are indispensable for tumor growth thus representing the best class of targets for cancer immunoprevention the study of immunopreventive vaccines_against subsequent phases of neoplastic progression showed dramatic loss of efficacy against established mammary carcinomas whereas the prevention of micrometastasis growth was successful preclinical results provide useful indications for the translation of cancer immunoprevention to humans and useful hints for cancer immunotherapy

25228655

Antitumor efficacy of a bispecific antibody that targets HER2 and activates T cells.
Teemu T Junttila, Ji Li, Jennifer Johnston, Maria Hristopoulos, Robyn Clark, Diego Ellerman, Bu-Er Wang, Yijin Li, Mary Mathieu, Guangmin Li, Judy Young, Elizabeth Luis, Gail Lewis Phillips, Eric Stefanich, Christoph Spiess, Andrew Polson, Bryan Irving, Justin M Scheer, Melissa R Junttila, Mark S Dennis, Robert Kelley, Klara Totpal, Allen Ebens
(Genentech, Inc., South San Francisco, California. junttila.teemu@gene.com.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.; Genentech, Inc., South San Francisco, California.)
Cancer Res.

clinical results from the latest strategies for t-cell activation in cancer have fired interest in combination immunotherapies that can fully engage t-cell_immunity in this_study we_describe trastuzumab-based bispecific_antibody her2-tdb which targets her2 and conditionally activates cells her2-tdb specifically killed her2-expressing cancer cells at low picomolar_concentrations because of its unique mechanism of action which is independent of her2 signaling or chemotherapeutic sensitivity her2-tdb eliminated cells refractory to currently_approved her2 therapies her2-tdb exhibited potent_antitumor activity in four preclinical model_systems including mmtv-huher2 and hucd3 transgenic_mice pd-l1 expression in tumors limited her2-tdb activity but this resistance could_be reversed by anti-pd-l1 treatment thus combining her2-tdb with anti-pd-l1 yielded combination immunotherapy that enhanced tumor growth_inhibition increasing the rates and durability of therapeutic response

20532501

Anti-HER2 vaccines: new prospects for breast cancer therapy.
Maha Zohra Ladjemi, William Jacot, Thierry Chardès, André Pèlegrin, Isabelle Navarro-Teulon
(IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U896, Université Montpellier1, Montpellier, France.)
Cancer Immunol. Immunother.

each_year breast cancer accounts_for more_than new cancer cases and more_than cancer deaths in europe prognosis of nonmetastatic breast cancer patients is directly_related to the extent of the disease mainly nodal spreading and tumor_size and to the molecular profile particularly her2 over-expression in patients with her2-over-expressing tumors different studies have_shown cellular and/or humoral_immune responses against her2 associated_with lower tumor development at early_stages of the disease these_findings have led to the hypothesis that the generation of an anti-her2 immune_response should protect patients from her2-over-expressing tumor growth taken_together with the clinical efficiency of trastuzumab-based anti-her2 passive_immunotherapy these_observations allowed to envisage various vaccine_strategies against her2 the induction of stable and strong immunity by cancer vaccines is expected to lead to establishment of immune memory thereby_preventing tumor recurrence however an immunological_tolerance against her2 antigen exists representing barrier to effective vaccination_against this oncoprotein as_consequence the current challenge for vaccines is to find the best conditions to break this immunological_tolerance in this_review we will_discuss the different anti-her2 vaccine_strategies currently developed considering the strategies having reached the clinical phases as_well as those still in preclinical development the used antigen can_be either composed of tumoral allogenic cells or autologous cells or specific to her2 it can_be delivered by dendritic_cells or in dna peptidic or proteic form another area of research concerns the use of anti-idiotypic antibodies mimicking her2

11358826

Phagocytosis of breast cancer cells mediated by anti-MUC-1 monoclonal antibody, DF3, and its bispecific antibody.
C Akewanlop, M Watanabe, B Singh, M Walker, D W Kufe, D F Hayes
(The Breast Cancer Program, Lombardi Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington, DC 20007, USA.)
Cancer Res.

human epithelial_mucin muc-1 is commonly expressed in adenocarcinoma including of breast cancers erbb-2 is overexpressed in approximately of breast cancers expression of muc-1 and erbb-2 may_be partially_overlapping but discoordinate therefore combined use of antibodies_directed against these two antigens might increase the number of patients who benefit_from immunotherapy monoclonal_antibody mab_df3 recognizes the muc-1 tandem_repeat we_investigated phagocytosis and cytolysis of cultured human breast cancer cells by monocyte-derived_macrophages mediated_by mab_df3 and its bispecific_antibody bsab df3xh22 with the second epitope directed_against the fc component of phagocytic cells purified monocytes from healthy_donors were cultured with granulocyte_macrophage colony-stimulating_factor with or without ifn-gamma antibody-dependent_cellular phagocytosis adcp and antibody-dependent_cellular cytotoxicity_adcc assays were performed with these macrophages and muc-1-expressing target cells zr75-1 in the presence of mab_df3 and bsab df3xh22 adcp was measured by two-color_fluorescence flow_cytometry using pkh2 green_fluorescent dye and r-phytoerythrin rpe red conjugated mab against human cd14 and cd11b and was confirmed by confocal_microscopy adcc was measured by cr release assay immunohistochemical_staining studies of muc-1 and erbb-2 were performed on primary breast cancer tissues expression of muc-1 and erbb-2 was partially_overlapping but discoordinate in consecutive breast cancers both mab_df3 and bsab df3xh22 mediated adcp however adcp mediated_by mab_df3 was greater_than that mediated_by bsab df3xh22 adcc as detected by cr release was not seen with either antibody the addition of ifn-gamma to monocyte-derived macrophage cultures inhibited adcp compared to granulocyte_macrophage colony-stimulating_factor alone given the partially_overlapping but discoordinate expression of muc-1 and erbb-2 in breast cancer therapy directed_toward both antigens should_be considered mab_df3 and the bsab df3xh22 can effectively mediate phagocytosis of muc-1-expressing target cells further_investigations are_needed to determine_whether this antibody-induced phagocytosis results in long-term specific t-cell activation against muc-1

23792807

Functionalized nanospheres for targeted delivery of paclitaxel.
Jared Bushman, Asa Vaughan, Larisa Sheihet, Zheng Zhang, Marius Costache, Joachim Kohn
(New Jersey Center for Biomaterials and Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 145 Bevier Road, Piscataway, NJ 08854, USA.)
J Control Release

targeted_delivery of anti-cancer_agents to cancer cells is mature line of investigation that has yet to realize its full potential in this_study we_report on the development of delivery_platform with the future goal of merging two thus_far parallel methods for selective elimination of cancer cells targeted nanospheres and pretargeted radioimmunotherapy several clinical_trials have_shown the promise of pretargeted radioimmunotherapy which leverages the specificity of antibodies for targeted cell populations and delivers localized dose of biotinylated radionuclide that is most often administered following binding of biotinylated antibody and streptavidin sta to the target cells the work presented_here describes the development of biotinylated nanospheres based_on an aba-type copolymer comprised of tyrosine-derived oligomer as the b-block and poly_ethylene glycol_peg a-blocks the biotinylated nanospheres encapsulate paclitaxel_ptx to the same extent as unbiotinylated nanospheres efficacy of targeting was shown on cd44 positive cells in the sum159 breast cancer cell_line by_incubating the cells sequentially with biotinylated anti-cd44 antibody sta and the biotinylated nanospheres encapsulating ptx targeted nanospheres achieved the half_maximal inhibitory_concentration of ptx on sum159 cells at 5-10 fold lower concentration than that of ptx applied in either non-targeted nanospheres or free drug approaches moreover targeted nanospheres selectively eliminated cd44 positive sum159 cells compared to free_ptx and untargeted nanospheres this new_generation of nano-sized carrier offers versatile platform that can_be adopted for wide_variety of drug and target specific applications and has the potential to be combined with the clinically emerging method of pretargeted radioimmunotherapy

22354215

Flexible targeting of ErbB dimers that drive tumorigenesis by using genetically engineered T cells.
David M Davies, Julie Foster, Sjoukje J C Van Der Stegen, Ana C Parente-Pereira, Laura Chiapero-Stanke, George J Delinassios, Sophie E Burbridge, Vincent Kao, Zhe Liu, Leticia Bosshard-Carter, May C I Van Schalkwyk, Carol Box, Suzanne A Eccles, Stephen J Mather, Scott Wilkie, John Maher
(King's College London, King's Health Partners Integrated Cancer Center, Department of Research Oncology, Guy's Hospital Campus, London, UK.)
Mol. Med.

pharmacological targeting of individual erbb_receptors elicits antitumor_activity but is frequently compromised by resistance leading to therapeutic failure here_we describe an immunotherapeutic_approach that exploits prevalent and fundamental mechanisms by which aberrant upregulation of the erbb network drives_tumorigenesis chimeric_antigen receptor named t1e28z was engineered in which the promiscuous erbb ligand t1e is fused to cd28 cd3ζ endodomain using panel of erbb-engineered 32d hematopoietic cells we found that human t1e28z⁺ cells are selectively activated by all erbb1-based homodimers and heterodimers and by the potently mitogenic erbb2/3 heterodimer owing to this flexible targeting capability recognition and destruction of several tumor cell_lines was achieved by t1e28⁺ cells in vitro comprising wide_diversity of erbb_receptor profiles and tumor origins furthermore compelling antitumor_activity was observed in mice_bearing established xenografts characterized either by erbb1/2 or erbb2/3 overexpression and representative of insidious or rapidly_progressive tumor types together_these findings support the clinical development of broadly_applicable immunotherapeutic_approach in which the propensity of solid_tumors to dysregulate the extended erbb network is targeted for therapeutic gain