autologous blood and marrow transplantation - Blog Science ...

662 Chapter 13: Immunotherapy
Table 1. Tumor cells escape recognition by T cells
Tumor cells:
• Deficient or ineffective HLA expression
• Lack of immunogenic peptides
• Defective antigen processing
• Lack of costimulatory molecules
• Production of inhibitory compounds
T cells:
• Lack of zeta-chain of T-cell receptor
• Defective signal transduction pathways
However, the study is largely inconclusive as the protocol required the administration
of a relatively high dose of IL-2 that caused premature discontinuation of
the cytokine in the majority of patients.
Administration of interferon is problematic as it has side effects that can
interfere with the recovery of the patient early after bone marrow transplant. 5
It
may, however, have a clinical benefit particularly when combined with IL-2. 6
Cellular treatments are promising but often cumbersome to prepare. Leukemiaspecific
T cells can be generated when antigen-presenting cells such as dendritic
cells are used to generate specific T cells. Dendritic cells can be cultured from
CD34 cells or monocytes from blood, bone marrow, or cord blood sources. These
cells can be "spiked" with tumor antigens obtained by various methods (Table 3).
These engineered dendritic cells can be reinjected into autologous recipients or
used to expand T cells ex vivo. Clinical studies are underway using different
techniques of spiking dendritic cells.
Since NK/LAK cells recognize tumor targets that lack or have mutated MHC
antigens, they should theoretically be "broader" antitumor cells than T
lymphocytes, which require intact MHC in addition to presentation of a specific
antigen. The infusion of autologous LAK is tolerated early after transplant. 7
- 8
However, the process of obtaining and culturing LAK cells is cumbersome, and
patients require IL-2 injections to maintain their activity in vivo.
Table 2. Antitumor immunotherapy in autologous transplantation
Autologous GVHD
• Cytokines
• Ex vivo activation of autograft
• Monoclonal antibodies
• Immunization strategies
• Cellular therapies