Journal
BLOOD
Volume 118, Issue 4, Pages 946-954Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-325035
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [Sonderforschungsbereich TR36, KL 427/15-1]
- Helmholtz-Gemelnschaft Deutscher Forshcuncszentren [HA-202]
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Adoptive therapy with T-cell receptor (TCR)-engineered T cells is a promising approach in cancer treatment. While usage of T cells specific for tumor-associated antigens (TAAs) can lead to serious side effects because of autoimmunity, targeting true tumor-specific mutations, such as the products of translocations in leukemias, should reduce such a risk. A potentially ideal target might be the chimeric protein TEL-AML1, which results from the chromo-somal translocation 12; 21 and represents the most common fusion gene in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Within the fusion region of TEL-AML1, a single epitope has been described by reverse immunology as immunogenic in HLA-A* 0201 restriction settings. As a potential source of TCRs specific for this TEL-AML1 epitope, we have used mice expressing a human TCR-alpha beta repertoire and human MHC class I. Surprisingly, we have found that, although a specific functional CD8(+) T-cell response against this peptide could be evoked, the described epitope was in fact not endogenously processed. Analyses done with a potent antigen-presenting cell line, as well as with purified human proteasomes, support the conclusion that this peptide cannot be proposed as a potential target in immunotherapy of ALL in HLA-A* 0201-restricted fashion. (Blood. 2011;118(4):946-954)
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