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Adoptive TCR transfer against rapidly mutating targets, such as HIV-1 or cancer, must counteract corresponding immune escape. Hence, we generated T cells expressing two additional receptors (TETARs) specific for HIV-1 by TCR mRNA electroporation. An HLA-A2–restricted gag-specific TCR and an HLA-B13–restricted nef-specific TCR were chosen. When both TCRs were transfected simultaneously, strong competitive effects occurred that were overcome by replacing the human constant domains of one TCR with murine counterparts and adapting the amounts of TCR-RNA used for transfection. The resulting TETAR responded to both epitopes with cytokine secretion and cytotoxic function. Cell sorting revealed that one individual cell indeed recognized both epitopes. The T cells diminished their reactivity to each epitope after stimulation but sequentially killed targets that presented the gag epitope and then targets that presented the nef epitope, or vice versa. Taken together, TETARs represent a sophisticated tool to study TCR functionality and might be a useful strategy in immunotherapy.

No relevant conflicts of interest to declare.

Hilgendorf: Novartis: Other: Travel support, Research Funding; Medac: Other: Travel support, Research Funding.

Introduction:

Introduction:Post-transplant morbidity and mortality are majorly determined by GvL effect counter-balanced by GvHD. Treatment with systemic steroids represents the first-line therapy for GvHD, but is associated with increased incidence of infection and relapse. ECP can reduce the extent of GvHD while preserving anti-virus/-tumor activity. However, ECP, a time-consuming and relatively expensive therapy, requires specialized equipment and staff expertise as well as the mechanism of action remains unclear. Therefore, this study was performed to address these unsolved questions.

Introduction:Genetically modified T cells expressing chimeric antigen receptors (CARTs) are currently among the most encouraging treatment approaches in cancer immunotherapy. Efficacy and persistence of adoptively transferred CARTs are linked to the proportion of naïve-like T cells (TN) and stem cell memory-like (TSCM) T cells defined by stem cell-like properties such as a high proliferative and self-renewal capacity. Optimization of CART production is important to shift the balance towards these subsets. The PI3K/mTOR/AKT pathway is one of the main pathways involved in T cell differentiation. In the current study we evaluated the inhibition of PI3K by the clinically approved small molecule idelalisib during culturing of CARTs in order to increase less differentiated T cell subpopulations in the final cell product.

Wuchter: Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hexal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Dreger:Gilead: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Roche: Consultancy.

Introduction

Kuball: Gadeta B.V.: Membership on an entity's Board of Directors or advisory committees. Wuchter:Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hexal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Dreger:Gilead: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Roche: Consultancy. Greiner:BMS: Research Funding.

Introduction:Patients receiving an allogeneic stem cell graft from a cytomegalovirus (CMV) seronegative donor are prone to CMV reactivation with high risk of disease and mortality. Therefore we initiated a clinical phase I trial with a novel vaccine designed by our group: a CMV phosphoprotein 65 (CMVpp65)-derived peptide in water-in-oil emulsion (Montanide™) plus administration of granulocyte-macrophage colony stimulating factor.