ThinkTank, is a free knowledge community focused on the antibody engineering field. Ask questions. Share answers. And boost your reputation. IBC Life Sciences, producer of the Antibody Engineering & Therapeutics conference, hosts these conversations to enable efficient knowledge exchange amongst practitioners. Insight is within sight.
ThinkTank has been built for professionals in a mobile world, who need high-quality answers to difficult questions from people with experience and expertise.
One of the many industry experts who actively participate on ThinkTank is Paul Parren, Ph.D., Senior Vice President and Scientific Director, Genmab, The Netherlands – Below you will find snippets of his responses to a variety of questions that have been posed on the platform. To continue your learnings with the Antibody Engineering community, be sure to login to ThinkTank now.
Excerpts from Dr. Parren's insights via ThinkTank;
With all the different antibody modalities to choose from (bispecifics, antibody fragments, antibody mixtures, ADCs and other conjugations, fusions, antibody combinations), how does one decide which approach to use in a specific project? And what are some advantages and disadvantages of these various modalities?
Dr. Parren: Your approach would be guided by the target product profile, i.e. does your application require long/short half-life, antibody effector function yes/no etc. This should eliminate a number of the possibilities. Then the approach becomes empirical in which I would recommend to produce a model antibody in a number of the remaining formats and assess for maximal activity/safety in comparison to competitor drugs.
Which immunotherapeutic antibody mechanisms have shown the most promise in the clinic? And where is this field headed next?
Dr. Parren: Hard to say in general. Preferably a therapeutic antibody engages multiple mechanisms as a single specific mechanism may, for example, not work against all diseased cells or in all anatomical niches. The required mechanisms will in addition be strongly dependent on your intended application.
The development future of non-canonical therapeutic antibodies (such as nanobodies, antibody scaffolds)?
Dr. Parren: This is a very broad question and therefore not easy to answer in general terms. In my opinion, antibody fragments such as nanobodies, will have their strongest appeal in areas not served by classical, full length, antibodies. That is in areas for which topical or local administration is most appropriate. One could think of ocular injection or inhalation. In addition, applications which require a short in vivo half-life are attractive, e.g. imaging or in which short, temporary, target inhibition is important.
Should patients be pre-screened (genetically or epigentically) in order to achieve the maximum efficiency/efficacy of antibody therapy?
Dr. Parren: Prescreening of patients to be treated with targeted therapies is important to achieve maximal effects and proper patient selection is the future. Choosing the right biomarker or companion diagnostic will be critical however. Genetic prescreening may only be suitable for some applications, i.e. when screening for target expression, an antibody-based diagnostics may be more appropriate. The impact of the microbiome on antibody therapy is a relatively new field, which needs substantial further investigation, but definitely an area to watch.
The current therapeutic antibodies are targeting membrane-bound or circulating proteins. Any efforts or prospects on targeting intracelluar proteins using antibody/derivatives?
Dr. Parren: The best progress on targeting intracellular proteins is in the targeting of MHC-peptide (e.g. WT1 and NY-ESO-1) complexes presented on the surface of tumor cells with antibodies or affinity-matured TCR antibody-like constructs. Several groups are trying to target antibodies to intracellular compartments, but none of these efforts is ready for prime time yet.
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