6th Annual European Antibody Congress 2010: November 29–December 1, 2010, Geneva,Switzerland

The 6^th European Antibody Congress (EAC), organized by Terrapinn Ltd., was held in Geneva, Switzerland, which was also the location of the 4^th and 5^th EAC.^1,2 As was the case in 2008 and 2009, the EAC was again the largest antibody congress held in Europe, drawing nearly 250 delegates in 2010. Numerous pharmaceutical and biopharmaceutical companies active in the field of therapeutic antibody development were represented, as were start-up and academic organizations and representatives from the US Food and Drug Administration (FDA). The global trends in antibody research and development were discussed, including success stories of recent marketing authorizations of golimumab (Simponi^®) and canakinumab (Ilaris^®) by Johnson & Johnson and Novartis, respectively, updates on antibodies in late clinical development (obinutuzumab/GA101, farletuzumab/MORAb-003 and itolizumab/T1 h, by Glycart/Roche, Morphotek and Biocon, respectively) and success rates for this fast-expanding class of therapeutics (Tufts Center for the Study of Drug Development). Case studies covering clinical progress of girentuximab (Wilex), evaluation of panobacumab (Kenta Biotech), characterization of therapeutic antibody candidates by protein microarrays (Protagen), antibody-drug conjugates (sanofi-aventis, ImmunoGen, Seattle Genetics, Wyeth/Pfizer), radio-immunoconjugates (Bayer Schering Pharma, Université de Nantes) and new scaffolds (Ablynx, AdAlta, Domantis/GlaxoSmithKline, Fresenius, Molecular Partners, Pieris, Scil Proteins, Pfizer, University of Zurich) were presented. Major antibody structural improvements were showcased, including the latest selection engineering of the best isotypes (Abbott, Pfizer, Pierre Fabre), hinge domain (Pierre Fabre), dual antibodies (Abbott), IgG-like bispecific antibodies (Biogen Idec), antibody epitope mapping case studies (Eli Lilly), insights in FcγRII receptor (University of Cambridge), as well as novel tools for antibody fragmentation (Genovis). Improvements of antibody druggability (Abbott, Bayer, Pierre Fabre, Merrimack, Pfizer), enhancing IgG pharmacokinetics (Abbott, Chugai), progress in manufacturing (Genmab, Icosagen Cell Factory, Lonza, Pierre Fabre) and the development of biosimilar antibodies (Biocon, Sandoz, Triskel) were also discussed. Last but not least, identification of monoclonal antibodies (mAbs) against new therapeutic targets (Genentech, Genmab, Imclone/Lilly, Vaccinex) including Notch, cMet, TGFβRII, SEMA4D, novel development in immunotherapy and prophylaxis against influenza (Crucell), anti-tumor activity of immunostimulatory antibodies (MedImmune/Astra Zeneca) and translations to clinical studies including immunogenicity issues (Amgen, Novartis, University of Debrecen) were presented.Key words: therapeutic antibodies, antibody-drug conjugates, protein scaffolds, biosimilars, bioproduction

• MAbs. 2011 Mar-Apr; 3(2): 111–132.
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• Day 1: November 29, 2010

2011 Mar-Apr; 3(2): 111–132. Published online 2011 Mar 1. doi: 10.4161/mabs.3.2.14788

Day 1: November 29, 2010

Alain Beck Copyright and License information DisclaimerCopyright notice The EAC chairman, Alain Beck (Centre d''Immunologie Pierre Fabre), opened the meeting with a presentation on strategies and challenges for the next generation of therapeutic antibodies.³ By analyzing the regulatory approvals of IgG-based biotherapeutic agents in the past ten years, we can gain insights into the successful strategies used by pharmaceutical companies so far to bring innovative drugs to the market. Strategies to optimize the structure of IgG antibodies and to design related or new structures with additional functions were presented. A detailed knowledge of antibody structure and activity now allows researchers to engineer primary antibodies on a more rational basis. Most approved antibodies are chimeric, humanized or human IgGs with similar constant domains. Numerous studies looking at the structure-function relationships of these antibodies have been published in the past five years with the aim of identifying antibody microvariants⁴ and investigating the influence of these variants on antigen binding, stability, pharmacokinetics (PK) and pharmacodynamics (PD). This knowledge is now being used to increase homogeneity and mitigate the chemistry, manufacture and control (CMC) liabilities of preclinical antibody candidates by genetic engineering. The removal by mutation of instability or aggregation hot spots in the antibody complementarity-determining regions (CDRs), and the use of hinge-stabilized or aglycosylated IgG4, are just a few examples of antibodies with improved pharmacological properties, including decreased heterogeneity, that are currently in development.Dr. Beck explained that the variable fragment (Fv) of an antibody is responsible for interactions with antigens and dictates essential properties such as binding affinity and target specificity. The origin of the Fv in therapeutic antibodies can be diverse, e.g., hybridomas, human antibody libraries, rodents with a human antibody repertoire or primatized or humanized antibodies from various species. Affinity maturation allows the binding affinity of the Fv to be improved or target selectivity to be modulated. The constant fragment (Fc) of an antibody is responsible for interactions with immune cells, and the associated properties of the Fc can also be modulated by engineering at several levels:⁵ altering the glycosylation status to regulate anti- and pro-inflammatory properties, modulating antibody-dependent cellular cytotoxicity (ADCC) by site-directed mutagenesis to alter binding to Fc receptors, increasing the serum half-life by Fc engineering to increase binding to the neonatal Fc receptor (FcRn), thereby preventing IgG degradation, and increasing complement activation by isotype chimerism. Additional functions can be endowed on antibodies by conjugation to other drugs. To date, the clinical success of antibody-drug conjugates (ADCs) has been limited. Nevertheless, promising new ADCs that include linkers with optimized properties (e.g., hydrolysable in the cytoplasm, resistant or susceptible to proteases or resistant to multi-drug resistance efflux pumps) and highly cytotoxic drugs are being studied in advanced clinical trials (e.g., trastuzumab emtansine, inotuzumab ozogamicin and brentuximab vedotin).⁶ IgGs have also been engineered to contain unique drug conjugation positions to obtain uniform and more homogeneous drug conjugates, such as ThioMab-drug conjugates, which have a uniform stoichiometry of approximately two coupled drugs per antibody molecule. Collectively, these advances should open new therapeutic avenues to deliver highly cytotoxic drugs with increased tolerability.     

7th Annual European Antibody Congress 2011: November 29–December 1, 2011, Geneva,Switzerland

The 7^th European Antibody Congress (EAC), organized by Terrapin Ltd., was again held in Geneva, Switzerland, following on the tradition established with the 4^th EAC. The 2011 version of the EAC was attended by nearly 250 delegates who learned of the latest advances and trends in the global development of antibody-based therapeutics. The first day focused on advances in understanding structure-function relationships, choosing the best format, glycoengineering biobetter antibodies, improving the efficacy and drugability of mAbs and epitope mapping. On the second day, the discovery of novel targets for mAb therapy, clinical pipeline updates, use of antibody combinations to address resistance, generation and identification of mAbs against new targets and biosimilar mAb development were discussed. Antibody-drug conjugates, domain antibodies and new scaffolds and bispecific antibodies were the topics of the third day. In total, nearly 50 speakers provided updates of programs related to antibody research and development on-going in the academic, government and commercial sectors.Key words: therapeutic antibodies, antibody-drug conjugates, protein scaffolds, bispecific antibodies, biosimilar antibodies     

Influence of microbial activity on plant–microbial competition for organic and inorganic nitrogen

To investigate how the level of microbial activity in grassland soils affects plant–microbial competition for different nitrogen (N) forms, we established microcosms consisting of a natural soil community and a seedling of one of two co-existing grass species, Anthoxanthum odoratum or Festuca rubra. We then stimulated the soil microbial community with glucose in half of the microcosms and followed the transfer of added inorganic (¹⁵NH₄¹⁵NO₃) and organic (glycine-2-¹³C-¹⁵N) N into microbial and plant biomass. We found that microbes captured significantly more ¹⁵N in organic than in inorganic form and that glucose addition increased microbial ¹⁵N capture from the inorganic source. Shoot and root biomass, total shoot N content and shoot and root ¹⁵N contents were significantly greater for A. odoratum than F. rubra, whereas F. rubra had higher shoot and root N concentrations. Where glucose was not added, A. odoratum had higher shoot ¹⁵N content with organic than with inorganic ¹⁵N addition, whereas where glucose was added, both species had higher shoot ¹⁵N content with inorganic than with organic ¹⁵N. Glucose addition had equally negative effects on shoot growth, total shoot N content, shoot and root N concentrations and shoot and root ¹⁵N content for both species. Both N forms produced significantly more shoot biomass and higher shoot N content than the water control, but the chemical form of N had no significant effect. Our findings suggest that plant species that are better in capturing nutrients from soil are not necessarily better in tolerating increasing microbial competition for nutrients. It also appears that intense microbial competition has more adverse effects on the uptake of organic than inorganic N by plants, which may potentially have significant implications for interspecific plant–plant competition for N in ecosystems where the importance of organic N is high and some of the plant species specialize in use of organic N.     

9th Annual European Antibody Congress,November 11–13, 2013, Geneva,Switzerland

The annual European Antibody Congress (EAC) has traditionally been the key event for updates on critical scientific advances in the antibody field, and 2013 was no exception. Organized by Terrapinn, the well-attended meeting featured presentations on considerations for developing antibodies and antibody-like therapeutics, with separate tracks for antibody-drug conjugates, naked antibodies, and multispecific antibodies or protein scaffolds. The overall focus of the EAC was current approaches to enhance the functionality of therapeutic antibodies or other targeted proteins, with the ultimate goal being improvement of the safety and efficacy of the molecules as treatments for cancer, immune-mediated disorders and other diseases. Roundtable discussion sessions gave participants opportunities to engage in group discussions with industry leaders from companies such as Genmab, Glenmark Pharmaceuticals, MedImmune, Merrimack Pharmaceuticals, and Pierre Fabre. As the 2013 EAC was co-located with the World Biosimilar Congress, participants also received an update on European Medicines Agency guidelines and thoughts on the future direction and development of biosimilar antibodies in the European Union.     

11th European Cell Cycle Conference: April 23–26, 1997, Gardone Riviera (Italy) and Symposium on Cell Cycle Regulation (17th International Congress of Biochemistry and Molecular Biology): August 24–29, 1997, San Francisco,CA

In the following pages I have summarized some of the findings presented at two recent `cell cycle gatherings'. I have focused on those topics which in my opinion represent a substantial advancement in our understanding of the cell cycle regulatory pathways.     

Symposium on mammalian radiation genetics,July 7–9th, 1970 summary and synthesis

Papers given at the Symposium on Mammalian Radiation Genetics are summarized and discussed under three headings: (i) those helping to bridge the gap between what we know about genetic damage in the mouse and what we need to know in man; (ii) analytical studies on mice; (iii) assessment of genetic hazards from various sources.     

Relationship between copper biosorption and microbial inhibition of hydroxyl radical formation in a copper(II)–hydrogen peroxide system

The microbial retardation of the spin adduct, DMPO-OH, formed in a copper(II)–hydrogen peroxide–DMPO (5,5-dimethyl-1-pyrroline N-oxide) solution was examined in relation to copper biosorption. A hydroxyl radical is formed in the solution through two steps, the reduction of Cu(II) to Cu(I) by H₂O₂ and the Fenton-type reaction of Cu(I) with H₂O₂. The resultant radical is trapped by DMPO to form DMPO-OH. Microbial cells retarded the DMPO-OH in the Cu(II)–H₂O₂–DMPO far more significantly than in the UV-irradiated H₂O₂–DMPO solution. Egg albumin showed a higher DMPO-OH retardation than microbial cells both in the Cu(II)–H₂O₂–DMPO and the UV-irradiated H₂O₂–DMPO solutions. These results indicated that the retardation effect is related to organic matter and not to microbial activity. Microorganisms having higher affinities for copper ion retarded DMPO-OH more significantly. The linear relationship between the amounts of copper biosorption and the inverse of the median inhibitory doses for DMPO-OH indicated that the microbial cells inhibited the reduction of Cu(II) to Cu(I) by H₂O₂, followed by the decrease of hydroxyl radical formation and the retardation of DMPO-OH. These results also suggest that the coupling between microbial cells and Cu(II) ion can be estimated from their ability to retard DMPO-OH.