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Biology subjects

Atari, A.

Publications and source records attributed to Atari, A..

2 recordsLinked to original sources

Accelerating Cell Culture Media Development Using Bayesian Optimization-Based Iterative Experimental Design

Optimizing operational conditions for complex biological systems used in life sciences research and biotechnology is an arduous task. Here, we have applied a Bayesian Optimization-based iterative framework for experimental design to accelerate cell culture media development for two applications. First, we show this approach yields new compositions of media with cytokine supplementation to maintain the viability and distribution of PBMCs in culture. Second, we applied this framework to optimize the production of three recombinant proteins in K.phaffii cultivations. For both applications, we identified conditions with improved outcomes compared to the initial standard media using 3 to 30 times fewer experiments than other methods such as the Design of Experiments. Subsequently, we also demonstrated the extensibility of our approach to efficiently account for additional design factors through transfer learning. These examples demonstrate how coupling data collection, modeling, and optimization in this iterative paradigm, while using an exploration-exploitation tradeoff in each iteration, can reduce the time and resources for these types of optimizations.

bioengineering↗

Identification of potent biparatopic antibodies targeting FGFR2 fusion driven cholangiocarcinoma.

Translocations involving FGFR2 gene fusions are common in cholangiocarcinoma and predict response to FGFR kinase inhibitors. However, the rate and durability of response are limited due to the emergence of resistance, typically involving acquired FGFR2 kinase domain mutations, and to sub-optimal dosing, relating to drug adverse effects. Here, we report the development of biparatopic antibodies targeting the FGFR2 extracellular domain (ECD), as candidate therapeutics. Biparatopic antibodies can overcome drawbacks of standard bivalent monoparatopic antibodies, which often show poor inhibitory or even agonist activity against oncogenic receptors. We show that oncogenic transformation by FGFR2 fusions requires an intact ECD. Moreover, by systematically generating biparatopic antibodies that target distinct epitope pairs along the FGFR2 ECD, we identified antibodies that effectively block signaling and malignant growth driven by FGFR2-fusions. Importantly, these antibodies demonstrate efficacy in vivo, synergy with FGFR inhibitors, and activity against FGFR2 fusions harboring kinase domain mutations. Thus, biparatopic antibodies may serve as new treatment options for patients with FGFR2-altered cholangiocarcinoma. SummaryWe identify biparatopic FGFR2 antibodies that are effective against FGFR2 fusion driven cholangiocarcinoma.

cancer biology↗