title: Phage Display Engineered T Cell Receptors as Tools for the Study of Tumor Peptide-MHC Interactions.
abstract: Cancer immunotherapy has finally come of age, demonstrated by recent progress in strategies that engage the endogenous adaptive immune response in tumor killing. Occasionally, significant and durable tumor regression has been achieved. A giant leap forward was the demonstration that the pre-existing polyclonal T cell repertoire could be re-directed by use of cloned T cell receptors (TCRs), to obtain a defined tumor-specific pool of T cells. However, the procedure must be performed with caution to avoid deleterious cross-reactivity. Here, the use of engineered soluble TCRs may represent a safer, yet powerful, alternative. There is also a need for deeper understanding of the processes that underlie antigen presentation in disease and homeostasis, how tumor-specific peptides are generated, and how epitope spreading evolves during tumor development. Due to its plasticity, the pivotal interaction where a TCR engages a peptide/MHC (pMHC) also requires closer attention. For this purpose, phage display as a tool to evolve cloned TCRs represents an attractive avenue to generate suitable reagents allowing the study of defined pMHC presentation, TCR engagement, as well as for the discovery of novel therapeutic leads. Here, we highlight important aspects of the current status in this field.
authors: Nextera AS , Oslo , Norway ; Centre for Immune Regulation, Oslo University Hospital, University of Oslo , Oslo , Norway ; Department of Biosciences, University of Oslo , Oslo , Norway.
authors: Geir Åge
authors: GÅ
authors: Løset
authors: Nextera AS , Oslo , Norway.
authors: Gøril
authors: G
authors: Berntzen
authors: Nextera AS , Oslo , Norway.
authors: Terje
authors: T
authors: Frigstad
authors: Nextera AS , Oslo , Norway.
authors: Sylvie
authors: S
authors: Pollmann
authors: Centre for Immune Regulation, Oslo University Hospital, University of Oslo , Oslo , Norway.
authors: Kristin S
authors: KS
authors: Gunnarsen
authors: Centre for Immune Regulation, Oslo University Hospital, University of Oslo , Oslo , Norway ; Department of Biosciences, University of Oslo , Oslo , Norway.
authors: Inger
authors: I
authors: Sandlie
keywords: T cell receptor; antigen presentation; immunotherapy; phage display; tumor immunity
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