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Current autologous cell therapies, with blockbuster products on the market, have been leading for a decade to unprecedented clinical successes in patients with hematological malignancies. However, these patient-derived T-cell therapies are facing many challenges. The use of GMP iPSC lines to produce immune effector cells will reduce the complexity of the manufacturing process and will provide an unlimited source of starting material. The goal of the EVOcells Oncology platform is to offer a truly allogeneic cell therapy platform to treat a broad number of cancer patients with consistent quality and scalability of the final product. Besides, the versatility of our platform to produce different immune cell types combined to customized genetic engineering strategies will bring cell therapy to the level of personalized medicine. Our “off-the-shelf” cell therapy platform has already validated two pillars: iPSC-derived NK cells (iNK) and iPSC-derived Macrophages (iMACs). Through multiple genetic engineering strategies specific to each immune cell type, we are developing a comprehensive portfolio of cell therapy products to address specific tumor escape mechanism in liquid and solid tumors. Our initial effort aimed to develop these two innate immune cell types to propose efficacious cell therapies with an increased safety profile as they have low risk of graft-versus-host disease (GvHD) or CRS (Cytokine Release Syndrome). Thanks to the expression of a broad pattern of activatory receptors, iNK cells form Immunological Synapses with tumor cells leading in turn to efficient killing with and without addition of a CAR construct. Besides, we demonstrated the possibility to combine “naked” iNK cells with marketed therapeutic monoclonal antibodies (mAb) to further improve their efficacy. At the end of the differentiation process, iMACs are showing a M0 like phenotype with high plasticity allowing the in vitro differentiation of the cells towards either a M1 or a M2 polarization in response to the appropriate stimulations. iMACs produce key macrophages cytokines and are able to kill tumor cells via ADCP (Antibody-Dependent-Cell-Phagocytosis) mechanism when combined to a therapeutic mAb. Thanks to our collaboration with clinicians at the IUCT-Oncopole (Toulouse Cancer Hospital), we were able to identify appropriate cancer indications and further demonstrate in a translational fashion that both iNK and iMACs are able to kill primary resistant tumor cells which were isolated from patient’ samples. Taken together, these results are showing the versatility and the breadth of our EVOcells Oncology platform to produce a true arsenal of cell therapies and its potential for future clinical development. Citation Format: Michael Esquerré, Audrey Holtzinger, Nadja Wagner, Monika Braun, Mélanie Pichery, Stefanie Pfaender, Stephanie Sontag, Kathrin Haake, Michela Mirenda, Michael Paillasse, Davide Grandolfo, Chloé Beuraud, Mandy Richter, Philip Hublitz, Julien Bousquet, Marion Fabre, Mylène Gador, Daniel Sommermeyer, Tanja Schneider, Oriane Bombarde, Camille Esquerré, Loic Ysebaert, Fabien Despas, Matthias Austen, Andreas Scheel, Markus Dangl. EVOcells Oncology: Tailored genetic engineering of iPSC-derived immune effector cells and combination with the right biologic therapeutics result in optimal killing of primary tumor cells from patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3203.

Catalyst degradation in membrane electrode assemblies was studied by voltage cycling in hydrogen/air atmosphere. The loss of electrochemically active surface area (ECSA) was quantified by cyclic voltammetry. The influence of cycle duration and dwell time during square wave voltage cycling on catalyst degradation was investigated, as well as the effect of scan rate on ECSA loss during triangular wave voltage cycling. Degradation rates per voltage cycle increased with longer cycle duration and lower scan rate, while degradation rates normalized to operating time were approximately constant over a wide range of cycle lengths and scan rates. The results suggest that the formation of a (sub-)surface oxide layer and cathodic dissolution are important processes in the platinum dissolution mechanism.

In order to resolve substrate effects on the adlayer structure and structure formation and on the substrate–adsorbate and adsorbate–adsorbate interactions, we investigated the adsorption of thin films of the ionic liquid (IL) 1-butyl-1-methylpyrrolidinium-bis(trifluoromethylsulfonyl)imide [BMP][TFSA] on the close-packed Ag(111) and Au(111) surfaces by scanning tunneling microscopy, under ultra high vacuum (UHV) conditions in the temperature range between about 100 K and 293 K. At room temperature, highly mobile 2D liquid adsorbate phases were observed on both surfaces. At low temperatures, around 100 K, different adsorbed IL phases were found to coexist on these surfaces, both on silver and gold: a long-range ordered (‘2D crystalline’) phase and a short-range ordered (‘2D glass’) phase. Both phases exhibit different characteristics on the two surfaces. On Au(111), the surface reconstruction plays a major role in the structure formation of the 2D crystalline phase. In combination with recent density functional theory calculations, the sub-molecularly resolved STM images allow to clearly discriminate between the [BMP]+ cation and [TFSA]− anion.

The interaction between an adsorbed 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide, [BMP][TFSA], ionic liquid (IL) layer and a Ag(111) substrate, under ultrahigh-vacuum conditions, was investigated in a combined experimental and theoretical approach, by high-resolution scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and dispersion-corrected density functional theory calculations (DFT-D). Most importantly, we succeeded in unambiguously identifying cations and anions in the adlayer by comparing experimental images with submolecular resolution and simulated STM images based on DFT calculations, and these findings are in perfect agreement with the 1:1 ratio of anions and cations adsorbed on the metal derived from XPS measurements. Different adlayer phases include a mobile 2D liquid phase at room temperature and two 2D solid phases at around 100 K, i.e., a 2D glass phase with short-range order and some residual, but very limited mobility and a long-range ordered 2D crystalline phase. The mobility in the different adlayer phases, including melting of the 2D crystalline phase, was evaluated by dynamic STM imaging. The DFT-D calculations show that the interaction with the substrate is composed of mainly van der Waals and weak electrostatic (dipole-induced dipole) interactions and that upon adsorption most of the charge remains at the IL, leading to attractive electrostatic interactions between the adsorbed species.