T cell recognition of bcr/abl in healthy donors and in patients with chronic myeloid leukaemia

In chronic myeloid leukaemia (CML), peptides from the fusion region of bcr3/abl2 are likely to play a role in anti-leukaemic T cell immunity. We investigated whether T cells that recognize bcr/abl fusion peptides could be detected in healthy donors and CML patients. T cell responses against bcr3/abl2 fusion peptides were analysed by {gamma}-interferon enzyme-linked immunospot assays after prestimulation of peripheral blood mononuclear cells in the presence of anti-CD3-antibodies and interleukin-2. Our results suggest that the T cell repertoire contains bcr3/abl2-reactive T cells in CML patients who are in cytogenetic remission, but also in some healthy individuals

A recombinant anti‐carcinoembryonic antigen immunoreceptor with combined CD3ζ‐CD28 signalling targets T cells from colorectal cancer patients against their tumour cells

BACKGROUND AND AIMS: The prognosis of metastatic colorectal cancer is still poor, raising the need for alternative therapeutic approaches, particularly by manipulating the antitumour immune response. Advanced tumour stages, however, are frequently accompanied by functional T cell defects which may be critical for a T cell based anticancer immunotherapy. The aim of this study was to address whether T cells from colorectal cancer patients with advanced tumour stages can be specifically antigen activated against their autologous tumour cells. METHODS: T cells were isolated from colorectal cancer patients and retrovirally transduced to express a recombinant immunoreceptor that has an extracellular binding domain for carcinoembryonic antigen (CEA) and an intracellular CD3ζ signalling domain with and without CD28 costimulation for T cell activation. RESULTS: Peripheral blood T cells from colorectal cancer patients were successfully engineered to express the anti‐CEA immunoreceptor on the cell surface. On coincubation with autologous CEA(+) tumour cells, T cells with anti‐CEA immunoreceptor are specifically activated to secrete interferon γ (IFN‐γ) and to lyse autologous tumour cells whereas T cells without immunoreceptor are not. T cells equipped with combined CD3ζ‐CD28 signalling receptor are more efficiently activated to secrete IFN‐γ compared with T cells with CD3ζ signalling receptor. Induction of interleukin 2 secretion on targeting towards autologous tumour cells requires triggering of T cells by the CD3ζ‐CD28 costimulatory receptor. CONCLUSIONS: T cells from advanced colorectal cancer patients can be tumour specifically activated with high efficiency by engraftment with a combined CD3ζ‐CD28 immunoreceptor to break tolerance against autologous tumour cells