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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2811-2818.
Prepublished online as a Blood First Edition Paper on July 16, 2007; DOI 10.1182/blood-2007-01-068932.
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Submitted January 24, 2007
Accepted July 5, 2007
Cellular immune therapy of chronic lymphocytic leukemia
Arnon P. Kater*, Marinus H.J. van Oers, and Thomas J. Kipps
Department of Hematology, Academic Medical Center Amsterdam, Amsterdam, Netherlands
Division of Hematology & Oncology, UCSD Moores Cancer Center, University of California-San Diego School of Medicine, La Jolla, CA, United States
* Corresponding author; email: a.p.kater{at}amc.uva.nl.
Although chemotherapy can induce complete responses in patients with chronic lymphocytic leukemia (CLL), it is not considered curative. Treated patients generally develop recurrent disease requiring additional therapy, which can cause worsening immune dysfunction, myelosuppression, and selection for chemotherapy-resistant leukemia-cell subclones. Cellular immune therapy promises to mitigate these complications and potentially provide for curative treatment. Most experience with this is in the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT), in which graft-versus-leukemia (GvL) effects can be observed and shown responsible for long-term disease-free survival. However, use of allo-HSCT for CLL is limited because of the lack of suitable donors and the treatment-related morbidity/mortality for elderly patients, who constitute the majority at risk for developing this disease. The GvL effect, however, suggests there are specific CLL-associated antigens that could be targeted in autologous cellular immune therapy. Effective strategies for this will have to overcome the disease-related acquired immune deficiency and the capacity of the leukemia-cell to induce T-cell tolerance, thereby compromising the activity of even conventional vaccines in patients with this disease. We will discuss the different strategies being developed to overcome these limitations that might provide for effective cellular immune therapy of CLL.
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