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Targets for MAbs: innovative approaches for their discovery & validation, LabEx MAbImprove 6th antibody industrial symposium, June 25-26, 2018, Montpellier, France.

ABSTRACT: Monoclonal antibodies (mAbs) have revolutionized the treatment landscape in many disciplines of human medicine. To continue this exciting trend, sustained identification of new, validated and preferably functional targets are needed. However, this is the precise bottleneck in today's development of the next generation of therapeutic mAbs. Failures in translating a target into a successful therapeutic mAb are much more frequent than successes. Labex MAbImprove is a French-led consortium of academic laboratories jointly working on several aspects of the development of next-generation mAbs. The network organizes annual international meetings gathering academia and industry to discuss the different challenges faced in the therapeutic mAbs field. The 2018 symposium (also called AIS2018 and co-organized with MabDesign, the immunotherapy French industrial sector) focused on the discovery and validation of new targets for therapeutic mAbs. Key players from industry and academia outlined a number of exciting contributions, notably dealing with new innovations in the target discovery area, but also lessons learned from failures in the past. This report summarizes the talks presented at the AIS2018. We aim at broad dissemination of the most relevant, unpublished findings presented during the meeting, and hope to inspire all the contributors in this field to take new directions and bring about improvements.

SUBMITTER: Martineau P

PROVIDER: S-EPMC6601567 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Targets for MAbs: innovative approaches for their discovery & validation, LabEx MAbImprove 6<sup>th</sup> antibody industrial symposium, June 25-26, 2018, Montpellier, France.

Martineau Pierre P Watier Hervé H Pèlegrin Andre A Turtoi Andrei A

mAbs 20190516 5

Monoclonal antibodies (mAbs) have revolutionized the treatment landscape in many disciplines of human medicine. To continue this exciting trend, sustained identification of new, validated and preferably functional targets are needed. However, this is the precise bottleneck in today's development of the next generation of therapeutic mAbs. Failures in translating a target into a successful therapeutic mAb are much more frequent than successes. Labex MAbImprove is a French-led consortium of academ ...[more]

PMID: 31043141

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Project description:26Al-26Mg ages were determined for 14 anorthite-bearing chondrules from five different unequilibrated ordinary chondrites (UOCs) with low petrologic subtypes (3.00-3.05). In addition, oxygen three isotopes of these chondrules were also measured. The selected chondrules are highly depleted in alkali elements, and anorthite is the only mesostasis phase, though they show a range of mafic mineral compositions (Mg# 76-97 mole%) that are representative of chondrules in UOCs. The mean ∆17O values in these chondrules range from -0.44 ± 0.23‰ to 0.49 ± 0.15‰, in good agreement with previous studies of plagioclase-bearing chondrules from UOCs. Anorthite in all chondrules exhibit resolvable excess 26Mg (> 1.0 ± 0.4‰). Their inferred (27Al/26Al)0 range from (6.3 ± 0.7)×10-6 to (8.9 ± 0.3)×10-6 corresponding to a timescale for chondrule formation of 1.8 ± 0.04 Ma to 2.16 ± 0.12/0.11 Ma after CAIs using a canonical (27Al/26Al)0 value of 5.25×10-5. The ages from six chondrules in LL chondrites are restricted to between 1.8 Ma and 1.9 Ma, whereas eight chondrules in L chondrites show ages from 1.8 Ma to 2.2 Ma, including three chondrules at ~2.0 Ma and two chondrules at ~2.15 Ma. The inferred chondrule formation ages from this study are at the peak of those previously determined for UOC chondrules, though with much shorter durations. This is potentially due to the time difference between formation of anorthite-bearing chondrules and typical UOC chondrules with alkali-rich compositions. Alternatively, younger chondrules ages in previous studies could have been the result of disturbance to the Al-Mg system in glassy mesostasis even at the low degree of thermal metamorphism in the parent bodies. Nevertheless, the high precision ages from this study (with uncertainties from 0.04 Ma to 0.15 Ma) indicate that there was potentially more than one chondrule forming event represented in the studied population. Considering data from LL chondrites only, the restricted duration (≤0.1 Ma) of chondrule formation ages suggests an origin in high density environments that subsequently lead to parent body formation. However, the unusually low alkali contents of the studied chondrules compared to common alkali-rich chondrules could also represent earlier chondrule formation events under relatively lower dust densities in the disk. Major chondrule forming events for UOCs might have postdated or concurrent with the younger anorthite-bearing chondrule formation at 2.15 Ma after CAIs, which are very close to the timing of accretion of ordinary chondrite parent bodies that are expected from thermal evolution of ordinary chondrite parent bodies.

Dataset Information

Targets for MAbs: innovative approaches for their discovery & validation, LabEx MAbImprove 6th antibody industrial symposium, June 25-26, 2018, Montpellier, France.

Publications

Targets for MAbs: innovative approaches for their discovery & validation, LabEx MAbImprove 6<sup>th</sup> antibody industrial symposium, June 25-26, 2018, Montpellier, France.

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