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Chronic Lymphocytic Leukemia-reactive T Cells during Disease Progression and after Autologous Tumor Cell Vaccines¹

Division of Molecular and Cellular Biology, Research Institute, Sunnybrook and Women’s College Health Sciences Center, Toronto, Ontario, M4N 3M5 Canada [E. G., C. H., J. M., M. L., D. E. S.], and Department of Medicine, University of Toronto, Toronto, Ontario, Canada [R. B., N. L. B., K. I., D. E. S.]

Purpose: Tumor-reactive T cells were measured in patients with chronic lymphocytic leukemia (CLL) because vaccines that increase the activity of these cells might lead to better disease control.

Experimental Design: Proliferation and ELISPOT assays (for T cells producing IFN- after stimulation by CD40-activated CLL cells) were used to determine the prevalence of tumor-reactive T cells in 25 CLL patients at various stages of disease progression. The effects of vaccines, composed of autologous-oxidized tumor cells, on both the clinical course and tumor-reactive T-cell numbers were then determined in 2 patients.

Results: CLL-reactive T cells were found at frequencies of 10^-3 in 6 of 11 patients. Significant proliferation was found in 15 of 25 patients and correlated with clinical stage. The inability to measure CLL-reactive T cells in the remaining patients was not uniformly a result of generalized T-cell dysfunction or defective antigen presentation by CD40-activated CLL cells. CLL-reactive T-cell frequencies increased in response to vaccination with oxidized autologous tumor cells in a patient with preexisting CLL-reactive T cells but not in a patient where tumor-reactive T cells were undetectable in the ELISPOT assay.

Conclusions: Tumor-reactive T cells exist in some CLL patients (mainly during earlier stages of disease) and may potentially mediate therapeutic responses if their numbers and activation states can be sufficiently increased by tumor vaccines.

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