Journal
ONCOIMMUNOLOGY
Volume 1, Issue 7, Pages 1095-1103Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/onci.20954
Keywords
chronic myeloid leukemia; cross-presentation; GM-CSF; immune monitoring; K562; whole cell vaccine
Categories
Funding
- Department of Defense [W81XWH-07-1-0080]
- Miles and Eleanor Shore Award, NCI [5R21CA115043-2]
- Early Career Physician-Scientist Award of the Howard Hughes Medical Institute
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BCR-ABL(+) K562 cells hold clinical promise as a component of cancer vaccines, either as bystander cells genetically modified to express immunostimulatory molecules, or as a source of leukemia antigens. To develop a method for detecting T-cell reactivity against K562 cell-derived antigens in patients, we exploited the dendritic cell (DC)-mediated cross-presentation of proteins generated from apoptotic cells. We used UVB irradiation to consistently induce apoptosis of K562 cells, which were then fed to autologous DCs. These DCs were used to both stimulate and detect antigen-specific CD8(+) T-cell reactivity. As proof-of-concept, we used cross-presented apoptotic influenza matrix protein-expressing K562 cells to elicit reactivity from matrix protein-reactive T cells. Likewise, we used this assay to detect increased anti-CML antigen T-cell reactivity in CML patients that attained long-lasting clinical remissions following immunotherapy (donor lymphocyte infusion), as well as in 2 of 3 CML patients vaccinated with lethally irradiated K562 cells that were modified to secrete high levels of granulocyte macrophage colony-stimulating factor (GM-CS F). This methodology can be readily adapted to examine the effects of other whole tumor cell-based vaccines, a scenario in which the precise tumor antigens that stimulate immune responses are unknown.
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