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RAPID COMMUNICATION
Ex Vivo Generation of Human Anti-Pre-B Leukemia-Specific Autologous Cytolytic T Cells
Angelo A. Cardoso,
Mark J. Seamon,
Hernani M. Afonso,
Paolo Ghia,
Vassiliki A. Boussiotis,
Gordon J. Freeman,
John G. Gribben,
Stephen E. Sallan, and
Lee M. Nadler
From the Departments of Medical and Pediatric Oncology, Dana Farber Cancer Institute, and the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
In contrast to other neoplasms, antigen-specific autologous cytolytic T cells have not been detected in patients with human pre-B-cell leukemias. The absence of efficient B7 family (B7-1/CD80; B7-2/CD86) -mediated costimulation has been shown to be a major defect in tumor cells' capacity to function as antigen-presenting cells. We show here the generation of autologous anti-pre-B-cell leukemia-specific cytolytic T-cell lines from the marrows of 10 of 15 patients with pre-B-cell malignancies. T-cell costimulation via CD28 is an absolute requirement for the generation of these autologous cytolytic T cells (CTL). Although costimulation could be delivered by either bystander B7 transfectants or professional antigen-presenting cells (indirect costimulation), optimal priming and CTL expansion required that the costimulatory signal was expressed by the tumor cell (direct costimulation). These anti-pre-B-cell leukemia-specific CTL lysed both unstimulated and CD40-stimulated tumor cells from each patient studied but did not lyse either K562 or CD40-stimulated allogeneic B cells. Cytolysis was mediated by the induction of tumor cell apoptosis by CD8+ T cells via the perforin-granzyme pathway. Although we were able to generate anti-leukemia-specific CTL from the bone marrow, we were unable to generate such CTL from the peripheral blood of these patients. These studies show that antigen-specific CTL can be generated from the bone marrow of patients with pre-B-cell leukemias and these findings should facilitate the design of adoptive T-cell-mediated immunotherapy trials for the treatment of patients with B-cell precursor malignancies.
Blood, Vol. 90 No. 2 (July 15), 1997:
pp. 549-561
© 1997 by The American Society of Hematology.
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