The shared tumor associated antigen cyclin‐A2 is recognized by high‐avidity T‐cells

Abstract

Cyclin-A2, a key cell cycle regulator, has been shown to be overexpressed in various types of malignancies with little expression in normal tissue. Such tumor-associated genes potentially are useful targets for cancer immunotherapy. However, high-avidity cyclinspecific T cells are considered to be thymically deleted. We identified at least one nonameric HLA-A*0201 binding cyclin-A2 epitope by a reverse immunology approach. Using a highly efficient T-cell expansion system that is based on CD40-activated B (CD40-B) cells as sole antigen-presenting cells we successfully generated cyclin-A2 specific CTL from HLA-A*0201 1 donors. Interestingly, high-avidity cyclin-A2 specific CTL lines, which recognized peptide-pulsed and antigen expressing target cells, were indeed generated by stimulation with CD40-B cells when pulsed with low concentrations of peptide, whereas CD40-B cells pulsed at saturating concentrations could only induce low-avidity CTL, which recognized peptide-pulsed target cells only. One high-avidity CTL line was subcloned and CTL clones, whose peptide concentration required for half-maximal lysis were less than 1 nM, could lyse cyclin-A2 expressing tumor cells. Taken together, cyclin A2 is an attractive candidate for immune intervention in a significant number of cancer patients and high-avidity T cells can be readily generated using CD40-B cells as antigen-presenting cells. ' 2009 UICC

Induction of antigen‐specific effector‐phase tolerance following vaccination against a previously ignored B‐cell lymphoma

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A gene expression signature that correlates with CD8+T cell expansion in acute Epstein-Barr virus infection

“…Cyclin A2 (CCNA2) has been implicated in the pathogenesis of cancer and it is overexpressed in acute and chronic leukemia and lymphoma as well as several solid tumors (Paterlini et al, 1993). Cyclin A2 is an attractive candidate for immune intervention in a significant number of cancer patients and high avidity T cells can be readily generated using CD40-B cells as antigen-presenting cells (Kondo et al, 2009). CCNA2 could explain a part of cell cycle's role in AIM.…”