At Transimmune we are pioneering research into understanding how antigen presenting cells are activated in vivo and applying that knowledge to revitalize the use of such cells in immune therapies.
Manipulating the immune system as therapy
The human immune system is highly complex and specific. It dynamically balances recognition and clearance of both foreign and self disease-causing agents, while maintaining tolerance to normal, healthy cells and tissues. However, in rare cases the immunological balance fails, leading to tolerance towards disease-causing cells (e.g. cancer), or inappropriate reaction against healthy tissue (e.g. autoimmunity). The balance of tolerance and immune reaction is a controlled process, in which antigen presenting cells play a key role as a master switch of the immune system. Antigen presenting cells turn immunity and tolerance on and off in a highly specific manner. Thus in cases of disease, where the immunological balance has failed and needs to be re-established, antigen presenting cells are the ideal immunotherapy target.
Antigen Presenting Cells play a central role
Antigen presenting cells have long been prized as a therapeutic tool by clinical immunologists given their specificity and the broad-based effector cell response they trigger. To date, the performance of dendritic cells, particularly in immuno-oncology, has been disappointing. Transimmune believes the modest efficacy seen to date is in part due to the highly artificial way dendritic cells have been generated, and believes its physiologically derived antigen presenting cells can revolutionize immune-based therapies. The use of antigen presenting cells is expected to be highly complementary to both standard therapies and other immunotherapies currently being explored.
A unique source of unidirectional APCs
In the 1980s, Professor Edelson, the founder of the company, invented ECP by using a photo-activated chemotherapy to reduce the tumor burden of malignant T cells in refractory cutaneous T-cell lymphoma (CTCL) patients.
To great surprise, some of the ECP-treated CTCL patients developed strong, tumor-specific immune responses that could not be explained by a simple palliative reduction in malignant T cells. Nearly 30 years of research by Professor Edelson into this phenomenon has revealed that ECP inadvertently provides the conditions for the physiologic activation of antigen presenting cells. Once activated, in ECP the cells become a mix of immunogenic or tolerogenic antigen presenting cells, depending on the environmental challenge they experience. Professor Edelson has identified the critical variables controlling both the activation of the cells, and their channeling towards immunizing or tolerogenic fates.
Transimmune technology platform
Transimmune was founded to apply the findings of Professor Edelson’s research to a new generation of ex-vivo cellular immuno-therapies. The company has now developed a cell therapy that is able to rapidly generate personalized, biologically active antigen presenting cells that are, importantly, either immunogenic or tolerogenic. Transimmune has learned to separate these opposing processes from each other calling them Transimmunization and Transtolerization. The technology comprises a device and processing protocols that are able to investigate the critical variables behind the generation of such bespoke antigen presenting cells and test them in various preclinical settings.
Applications of the technology
As a first step, Transimmune has successfully demonstrated the efficacy and safety of its Transimmunization technology platform in four different solid tumor murine models. Early proof of principle has also been achieved for Transtolerization in two different mouse models. The potential clinical fields of application of Transimmune’s cells are very broad, ranging from cancer and viral disease (Transimmunization) to transplantation and autoimmune disease (Transtolerization). The platform is designed to be scalable from mouse studies to human clinical trials.
Kibbi N, Sobolev O, Girardi M, Edelson RL. Induction of anti-tumor CD8 T cell responses by experimental ECP-induced human dendritic antigen presenting cells. Transfusion and Apheresis Science 2016, article in press.
Edelson RL. Mechanistic insights into extracorporeal photochemotherapy: Efficient induction of monocyte-to-dendritic cell maturation. Transfusion and Aperesis Science 50,3:322-329, 2014
Durazzo TS, Tigelaar RE, Filler R, Hayday A, Girardi, M, Edelson RL. Induction of monocte-to-dendritic cell maturation by extracorporeal photochemotherapy: Initiation via direct platelet signaling. Transfusion and Aperesis Science 50,3:370-378, 2014
Gonzalez AL, Berger CL, Remington J, Girardi M, Tigelaar RE, Edelson RL. Integrin-driven monocyte to dendritic cell conversion in modified extracorporeal photochemotherapy. Clin Exp Immunol 2014, 175(3): 449-57.
Futterleib JS, Feng H, Tigelaar, RE, Choi J, Edelson RL. Activation of GILZ gene by photoactivated 8-methoxypsoralen. Potential role of immunoregulatory dendritic cells in extracorporeal photochemotherapy. Transfusion and Aperesis Science 2014 50(3): 379-387.
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