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“Artificial Antigen Presenting Cell-based expansion of allogenic CD4+ Virus Specific T cells: towards a new generation of Adoptive Cell Therapies” (aAPC-4VST)

Personalized therapy, immunotherapy and cancer

Senior Researcher : Miguel Alvaro Benito

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Research Centre or Institution : Universidad Complutense de Madrid

Abstract

In aAPC-4VST we aim at applying concepts of basic research to face the impact of viral infections on immune suppressed patients. CMV and EBV stablish a latent infection by integrating their DNA in the host´s genome, reaching an incidence of 60-90% of the human population. Poor immune control of these viruses, resulting from immune suppression required in transplantation is associated to severe morbidities, hence life-threatening conditions. Adoptive Cell Therapies (ACT) based on Virus Specific T cells (VST) are considered the safest and most effective treatment against these viruses, and CD4+ T cells are key orchestrators of the mechanisms involved. Moreover, early reconstitution of this immune cellular compartment is associated with improved prognosis for Haematological Cell Transplantation (HCT).

However, despite the great clinical potential of CD4+ VSTs, there is no universal and/or straight pipeline for the expansion of these cells. We tackle the issue by assessing immunodominance patterns vs. these viruses and expanding VSTs applying an artificial Antigen Presenting Cell (aAPC) platform. Validation of such adaptable and versatile platform will have a direct impact on posttransplant treatments. Moreover, we envision a direct broader applicability of the platform considering the incidence and impact of CMV and EBV infections in other immune suppressed patients (chemotherapy or elders).

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