SofaGym: An open platform for Reinforcement Learning based on Soft Robot simulations

International audienceOpenAI Gym is one of the standard interfaces used to train Reinforcement Learning (RL) Algorithms. The Simulation Open Framework Architecture (SOFA) is a physics based engine that is used for soft robotics simulation and control based on real-time models of deformation. The aim of this paper is to present SofaGym, an open source software to create OpenAI Gym interfaces, called environments, out of soft robot digital twins.The link between soft robotics and RL offers new challenges for both fields: representation of the soft robot in a RL context, complex interactions with the environment, use of specific mechanical tools to control soft robots, transfer of policies learned in simulation to the real world, etc. The article presents the large possible uses of SofaGym to tackle these challenges by using RL and planning algorithms. This publication contains neither new algorithms nor new models but proposes a new platform, open to the community, that offers non existing possibilities of coupling RL to physics based simulation of soft robots. We present 11 environments, representing a wide variety of soft robots and applications, we highlight the challenges showcased by each environment. We propose methods of solving the task using traditional control, RL and planning and point out research perspectives using the platform

SofaGym: An open platform for Reinforcement Learning based on Soft Robot simulations

International audienceOpenAI Gym is one of the standard interfaces used to train Reinforcement Learning (RL) Algorithms. The Simulation Open Framework Architecture (SOFA) is a physics based engine that is used for soft robotics simulation and control based on real-time models of deformation. The aim of this paper is to present SofaGym, an open source software to create OpenAI Gym interfaces, called environments, out of soft robot digital twins.The link between soft robotics and RL offers new challenges for both fields: representation of the soft robot in a RL context, complex interactions with the environment, use of specific mechanical tools to control soft robots, transfer of policies learned in simulation to the real world, etc. The article presents the large possible uses of SofaGym to tackle these challenges by using RL and planning algorithms. This publication contains neither new algorithms nor new models but proposes a new platform, open to the community, that offers non existing possibilities of coupling RL to physics based simulation of soft robots. We present 11 environments, representing a wide variety of soft robots and applications, we highlight the challenges showcased by each environment. We propose methods of solving the task using traditional control, RL and planning and point out research perspectives using the platform

SofaGym: An open platform for Reinforcement Learning based on Soft Robot simulations

International audienceOpenAI Gym is one of the standard interfaces used to train Reinforcement Learning (RL) Algorithms. The Simulation Open Framework Architecture (SOFA) is a physics based engine that is used for soft robotics simulation and control based on real-time models of deformation. The aim of this paper is to present SofaGym, an open source software to create OpenAI Gym interfaces, called environments, out of soft robot digital twins.The link between soft robotics and RL offers new challenges for both fields: representation of the soft robot in a RL context, complex interactions with the environment, use of specific mechanical tools to control soft robots, transfer of policies learned in simulation to the real world, etc. The article presents the large possible uses of SofaGym to tackle these challenges by using RL and planning algorithms. This publication contains neither new algorithms nor new models but proposes a new platform, open to the community, that offers non existing possibilities of coupling RL to physics based simulation of soft robots. We present 11 environments, representing a wide variety of soft robots and applications, we highlight the challenges showcased by each environment. We propose methods of solving the task using traditional control, RL and planning and point out research perspectives using the platform

Measles virus-vaccine infected tumor cells induce tumor antigen cross-presentation by human plasmacytoid dendritic cells

International audiencePurpose: Plasmacytoid dendritic cells (pDC) are antigen-presenting cells specialized in antiviral response. The measles virus vaccine (MV) is proposed as an antitumor agent to target and specifically kill tumor cells without infecting healthy cells. Experimental design: Here, we investigated, in vitro, the effects of MV-infected tumor cells on phenotype and functions of human pDC. We studied maturation and tumor antigen cross-presentation by pDC, exposed either to the virus alone, or to MV-infected or UV-irradiated tumor cells. Results: We found that only MV-infected cells induced pDC maturation with a strong production of IFN-α, whereas UV-irradiated tumor cells were unable to activate pDC. This IFN-α production was triggered by the interaction of MV ssRNA with TLR7. We observed that MV-infected tumor cells were phagocytosed by pDC. Interestingly, we showed cross-presentation of the tumor antigen, NYESO-1, to a specific CD8+ T-cell clone, when pDC were cocultured with MV-infected tumor cells, whereas pDC were unable to cross-present NYESO-1 after coculture with UV-irradiated tumor cells. Conclusions: Altogether, our results suggest that the use of MV in antitumor virotherapy induces immunogenic tumor cell death, allowing pDC to mature, produce high amounts of IFN-α, and cross-present tumor antigen, thus representing a mode of recruiting these antigen presenting cells in the immune response

Cross-presentation of synthetic long peptides by human dendritic cells: a process dependent on ERAD component p97/VCP but Not sec61 and/or Derlin-1.

Antitumor vaccination using synthetic long peptides (SLP) is an additional therapeutic strategy currently under development. It aims to activate tumor-specific CD8(+) CTL by professional APCs such as DCs. DCs can activate T lymphocytes by MHC class I presentation of exogenous antigens - a process referred to as "cross-presentation". Until recently, the intracellular mechanisms involved in cross-presentation of soluble antigens have been unclear. Here, we characterize the cross-presentation pathway of SLP Melan-A16-40 containing the HLA-A2-restricted epitope26-35 (A27L) in human DCs. Using confocal microscopy and specific inhibitors, we show that SLP16-40 is rapidly taken up by DC and follows a classical TAP- and proteasome-dependent cross-presentation pathway. Our data support a role for the ER-associated degradation machinery (ERAD)-related protein p97/VCP in the transport of SLP16-40 from early endosomes to the cytoplasm but formally exclude both sec61 and Derlin-1 as possible retro-translocation channels for cross-presentation. In addition, we show that generation of the Melan-A26-35 peptide from the SLP16-40 was absolutely not influenced by the proteasome subunit composition in DC. Altogether, our findings propose a model for cross-presentation of SLP which tends to enlarge the repertoire of potential candidates for retro-translocation of exogenous antigens to the cytosol

Alpha particles induce anti-tumour immunity

The aim of this investigation is to determine whether irradiation of tumours with alpha radiation can foster an anti-tumour immune response.JRC.E.5-Nuclear chemistr

Alpha Particles Induce Autophagy in Multiple Myeloma Cells

International audienceOBJECTIVES: Radiation emitted by the radionuclides in radioimmunotherapy (RIT) approaches induce direct killing of the targeted cells as well as indirect killing through the bystander effect. Our research group is dedicated to the development of α-RIT, i.e., RIT using α-particles especially for the treatment of multiple myeloma (MM). γ-irradiation and β-irradiation have been shown to trigger apoptosis in tumor cells. Cell death mode induced by (213)Bi α-irradiation appears more controversial. We therefore decided to investigate the effects of (213)Bi on MM cell radiobiology, notably cell death mechanisms as well as tumor cell immunogenicity after irradiation.METHODS: Murine 5T33 and human LP-1 MM cell lines were used to study the effects of such α-particles. We first examined the effects of (213)Bi on proliferation rate, double-strand DNA breaks, cell cycle, and cell death. Then, we investigated autophagy after (213)Bi irradiation. Finally, a coculture of dendritic cells (DCs) with irradiated tumor cells or their culture media was performed to test whether it would induce DC activation.RESULTS: We showed that (213)Bi induces DNA double-strand breaks, cell cycle arrest, and autophagy in both cell lines, but we detected only slight levels of early apoptosis within the 120 h following irradiation in 5T33 and LP-1. Inhibition of autophagy prevented (213)Bi-induced inhibition of proliferation in LP-1 suggesting that this mechanism is involved in cell death after irradiation. We then assessed the immunogenicity of irradiated cells and found that irradiated LP-1 can activate DC through the secretion of soluble factor(s); however, no increase in membrane or extracellular expression of danger-associated molecular patterns was observed after irradiation.CONCLUSION: This study demonstrates that (213)Bi induces mainly necrosis in MM cells, low levels of apoptosis, and autophagy that might be involved in tumor cell death

Radio- immunothérapie alpha : Principes et intérêts en immunité antitumorale

International audience> La radioimmunothérapie alpha (RITα) est une thérapie anticancéreuse vectorisée utilisant généralement un anticorps monoclonal spécifique d'un antigène tumoral couplé à un émetteur de particules α. Les émetteurs α représentent un outil idéal pour éradiquer les tumeurs disséminées ou les métastases. De récentes données démontrent que les rayonnements ionisants, en plus de leur cytotoxicité directe, peuvent aussi induire une immunité antitumorale efficace. Les effets biologiques de l'irradiation pourraient donc être utilisés pour potentialiser la réponse à différents types d'immunothérapie, et ainsi ouvrir la voie au développement de nouvelles thérapies combinant RITα et immunothérapies. < radionucléide. Le choix du radionu-cléide repose sur des considérations pratiques (le coût, la disponibilité, le type de techniques de radiomar-quage et la facilité d'utilisation), le type d'émission du radioélément, le transfert d'énergie linéique (TEL : quantité d'énergie transférée au milieu par la particule incidente, par unité de longueur de la trajectoire en keV 1 /µm) et la demi-vie physique du radioisotope (durée nécessaire pour que la moitié des noyaux radioactifs d'une source se soient désintégrés) [2]. Cette dernière doit être, autant que possible, en adéquation avec la pharmacocinétique du vecteur utilisé, afin de délivrer la plus grande dose possible de radioactivité à la tumeur après l'injection. Une demi-vie trop courte entraînera un nombre élevé de désintégrations avant d'atteindre la cible. À l'inverse, une demi-vie trop longue engendrera un grand nombre de désintégrations du radionucléide pendant la phase d'éli-mination du vecteur, rendant le radioimmunoconjugué plus toxique. La demi-vie doit également être compatible avec les applications cliniques et la prise en charge du patient. Ainsi, le temps nécessaire au transfert du radionucléide du site de production jusqu'à l'hôpital, 1 1 keV (kiloélectronvolts) = 10 3 eV ; 1 MeV (megaélectonvolts) = 10 6 eV

Antitumor Immunity Induced after α Irradiation

Radioimmunotherapy (RIT) is a therapeutic modality that allows delivering of ionizing radiation directly to targeted cancer cells. Conventional RIT uses β-emitting radioisotopes, but recently, a growing interest has emerged for the clinical development of α particles. α emitters are ideal for killing isolated or small clusters of tumor cells, thanks to their specific characteristics (high linear energy transfer and short path in the tissue), and their effect is less dependent on dose rate, tissue oxygenation, or cell cycle status than γ and X rays. Several studies have been performed to describe α emitter radiobiology and cell death mechanisms induced after α irradiation. But so far, no investigation has been undertaken to analyze the impact of α particles on the immune system, when several studies have shown that external irradiation, using γ and X rays, can foster an antitumor immune response. Therefore, we decided to evaluate the immunogenicity of murine adenocarcinoma MC-38 after bismuth-213 (213Bi) irradiation using a vaccination approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a protective antitumor response that is mediated by tumor-specific T cells. The molecular mechanisms potentially involved in the activation of adaptative immunity were also investigated by in vitro studies. We observed that 213Bi-treated MC-38 cells release “danger signals” and activate dendritic cells. Our results demonstrate that α irradiation can stimulate adaptive immunity, elicits an efficient antitumor protection, and therefore is an immunogenic cell death inducer, which provides an attractive complement to its direct cytolytic effect on tumor cells

Combining α-Radioimmunotherapy and Adoptive T Cell Therapy to Potentiate Tumor Destruction.

Ionizing radiation induces direct and indirect killing of cancer cells and for long has been considered as immunosuppressive. However, this concept has evolved over the past few years with the demonstration that irradiation can increase tumor immunogenicity and can actually favor the implementation of an immune response against tumor cells. Adoptive T-cell transfer (ACT) is also used to treat cancer and several studies have shown that the efficacy of this immunotherapy was enhanced when combined with radiation therapy. α-Radioimmunotherapy (α-RIT) is a type of internal radiotherapy which is currently under development to treat disseminated tumors. α-particles are indeed highly efficient to destroy small cluster of cancer cells with minimal impact on surrounding healthy tissues. We thus hypothesized that, in the setting of α-RIT, an immunotherapy like ACT, could benefit from the immune context induced by irradiation. Hence, we decided to further investigate the possibilities to promote an efficient and long-lasting anti-tumor response by combining α-RIT and ACT. To perform such study we set up a multiple myeloma murine model which express the tumor antigen CD138 and ovalbumine (OVA). Then we evaluated the therapeutic efficacy in the mice treated with α-RIT, using an anti-CD138 antibody coupled to bismuth-213, followed by an adoptive transfer of OVA-specific CD8+ T cells (OT-I CD8+ T cells). We observed a significant tumor growth control and an improved survival in the animals treated with the combined treatment. These results demonstrate the efficacy of combining α-RIT and ACT in the MM model we established