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Phase I Dose Escalation Study with the Lewis Y Carbohydrate Specific Humanized Antibody IGN311

Journal of Cancer Therapy 2011年第5期2卷 760-771页

作者： Daniel Oruzio Gunter Waxenecker Christoph Aulmann Bruno Markl theodor wagner Geert Mudde Manfred Schuster Norbert Eller Andrea Mayer Stefan Stranner Gottfried Himmler Hans Loibner Günter Schlimok Ralf Kircheis Andreas Nechansky Zentralklinikum AugsburgGermany Igeneon ViennaAustria AGES Pharmed ViennaAustria S-TARget ViennaAustria Apeiron ViennaAustria CDMS ViennaAustria Immatics TubingenGermany f-Star ViennaAustria ViroLogik ErlangenGermany Meridian Biopharmaceuticals ViennaAustria.

Purpose: Investigation of safety, tolerability, pharmacokinetics, and anti-tumor activity of the Lewis Y-specific, fully humanized monoclonal antibody (mAb) IGN311 in patients with Lewis Y positive tumors in a Phase I clinical trial. Experimental Design: Twelve patients (pts) were enrolled in an open-label, uncontrolled, dose escalating Phase I study. Three pts received 50 mg, three pts 100 mg and six pts 200 mg IGN311 by i.v. infusion on days 1 and 15. Blood samples were taken immediately before infusion, and 0.5, 4, 8, 24 hours post infusion, as well as on days 3, 5 and 8 after the first and second infusion, respectively, and day 29. A final visit was scheduled for day 43. Results: No drug related adverse events were observed in the 50 mg and 100 mg dose groups. Three out of six patients in the 200 mg dose group showed drug related adverse reactions with nausea, vomiting and hypotension in one patient (NCI CTC grade 3) being the dose limiting toxicities. t1/2 of IGN311 was ~20 days after second infusion of IGN311. Sera of patients receiving IGN311 were capable of lysing Lewis Y positive tumor cells in vitro by both, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Circulating tumor cells found in the peripheral blood in two out of twelve pts prior to treatment were reduced after treatment to below the quantification limit of the detection method. None of the patients showed an increase in the number of disseminated tumor cells during treatment period. Conclusions: The good safety and PK profile, the biological activity regarding CDC and ADCC mediated tumor cell lysis, and the elimination of circulating tumor cells warrant further clinical investigation of IGN311.

关键词： Passive Immunotherapy Therapeutic Monoclonal Antibody Disseminated Tumor Cells Phase I Study Lewis Y Carbohydrate HAHA (Human Anti-Human Antibodies)

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Impact of Molecular Shape on Supramolecular Copolymer Synthesis in Seeded Living Polymerization of Perylene Bisimides

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CCS Chemistry 2019年第5期1卷 598-613页

作者： Wolfgang wagner Marius Wehner Vladimir Stepanenko Frank Wurthner Center for Nanosystems Chemistry(CNC)and Bavarian Polymer Institute(BPI) Universitat WürzburgTheodor-Boveri-WegWürzburg 97074Germany Institut fur Organische Chemie Universitat WürzburgWurzburg 97074Germany

Supramolecular polymerization properties have been studied for a series of perylene bisimide(PBI)dyes containing identical hydrogen-bonding amide groups in imide positions but variable number or size of alkoxy substit... 详细信息

关键词： supramolecular polymer self-assembly living supramolecular polymerization block copoly-mers perylene bisimides

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Renal cell carcinoma escapes NK cell-mediated immune surveillance through the downregulation of DNAM-1

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Cancer Communications 2023年第7期43卷 855-859页

作者： Veronika Kremer Shi Yong Neo Yaxuan Liu Yi Chen Arnika Kathleen wagner Ying Yang Ziqing Chen Christina Seitz Nicholas Patrick Tobin Maarten Alexander Ligtenberg Evren Alici Xinsong Chen Felix Haglund Barbara Seliger Ulrika Harmenberg Eugenia Colón Ann-Helén Scherman Plogell Lisa Lei Liu Andreas Lundqvist Department of Oncology-Pathology Karolinska InstitutetStockholmSweden Singapore Immunology Network Agency for ScienceTechnology and ResearchSingaporeSingapore Department of Medicine Columbia University Irving Medical CenterNew YorkUSA Department of Medicine Huddinge Karolinska InstitutetStockholmSweden Department of Molecular Biology Princeton UniversityNew JerseyUSA Institute of Environmental Medicine Karolinska InstitutetStockholmSweden Department of Molecular Oncology The Netherlands Cancer InstituteAmsterdamNetherlands Institute for Medical Immunology Martin-Luther University Halle-WittenbergHalleGermany Institute of Translational Immunology Medical School Theodor FontaneBrandenburg an der Havel14770and Fraunhofer Institute for Cell Therapy and ImmunologyLeipzigGermany Department ofWomen’s and Children’s Health Karolinska Institutet and S:t Göran’s Hospital-UnilabsStockholmSweden Department of Urology Stockholm South General HospitalStockholmSweden

Dear Editor,The activating receptor DNAX accessory molecule-1(DNAM-1)plays an important role in T and natural killer(NK)cell-mediated cytotoxicity via the interaction with its ligands poliovirus receptor(PVR,CD155)and Nectin-2(CD112).Compared with peripheral blood NK cells,tumor-infiltrating NK cells show reduced expression of DNAM-1 across several solid tumors,including ovarian and breast cancer resulting in impaired NK cell *** studies reported an inverse correlation between DNAM-1 expression and its ligands in leukemic blasts and ovarian cancer[1].

关键词： impaired cancer killer

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