Journal
JOURNAL OF IMMUNOTHERAPY
Volume 31, Issue 2, Pages 121-131Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CJI.0b013e31815aaf24
Keywords
adoptive immunotherapy; CTL; leukemia; expander beads; dendritic cells; immunization; mouse
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Funding
- NCI NIH HHS [R01 CA72669] Funding Source: Medline
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Identification of dominant leukemia-associated neoantigens and favoring specific priming and subsequent expansion of T cells reactive to these antigens might harbor therapeutic potential. Here, a new strategy combines a specific T-cell activation step using tumor lysate-pulsed bone marrow-derived dendritic cells with a nonspecific large-scale expansion method. The leukemia cell line C1498 transduced with a potentially immunodominant antigen (ovalbumin) was used to track expansion and functionality of antigen-specific cytotoxic T cell (CTL), both in vitro and in vivo. Three times more leukemia-specific CTL could be generated when compared with the respective controls. CTL generated after increasing the antigen-specific T-cell precursor frequency in vitro cured up to 80% of mice bearing leukemia with the respective antigen (P < 0.005, as compared with controls). Alternatively, the yield of CTL reactive to a immunodominant neoantigen increased by factor 2 to 6 when T-cell donors were immunized with dendritic cell presenting the respective antigen. However, increasing the leukemia-reactive precursor frequency to a clinically exploitable level will be the key for the design of successful T-cell therapy trials.
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