The expression of tumor-associated antigens (TAAs) might play a critical role in the control of minimal residual disease (MRD) in acute myeloid leukemia (AML), and therefore might be associated with clinical outcome in AML. In a DNA microarray analysis of 116 AML samples, we found a significant correlation between high mRNA levels of G250/CA9 and longer overall survival (P ‫؍‬ .022), a similar trend with high mRNA levels of PRAME (P ‫؍‬ .103), and a hint for RHAMM/HMMR. In contrast, for other TAAs like WT1, TERT, PRTN3, BCL2, and LAMR1, we found no correlation with clinical outcome. High expression of at least 1 of the 3 TAAs, RHAMM/HMMR, PRAME, or G250/ CA9, provided the strongest favorable prognostic effect (P ‫؍‬ .005). Specific Tcell responses were detected in 8 (47%) of 17 patients with AML in complete remission for RHAMM/HMMR-R3 peptide, in 7 (70%) of 10 for PRAME-P3 peptide, and in 6 (60%) of 10 for newly characterized G250/CA9-G2 peptide, a significant increased immune response compared with patients with AML patients who had refractory disease (P < .001). Furthermore, we could demonstrate specific lysis of T2 cells presenting these epitope peptides.In conclusion, expression of the TAAs RHAMM/HMMR, PRAME, and G250/CA9 can induce strong antileukemic immune responses, possibly enabling MRD control. Thus, these TAAs represent interesting targets for polyvalent immunotherapeutic approaches in AML. IntroductionTumor-associated antigens (TAAs) have been shown to induce specific T-cell immune responses in tumor patients, and thus represent potential target structures for specific immunotherapies. [1][2][3][4] Recently, a large number of TAAs inducing specific T-cell responses have been identified and functionally characterized in different solid tumors, but several TAAs also seem to be expressed in hematologic malignancies like acute myeloid leukemia (AML). 5,6 AML is the most common acute leukemia in adults. With intensive induction therapy, complete remission (CR) rates between 65% and 75% are achieved in younger patients (Ͻ 60 years). However, more than 50% of these patients will relapse, leading to an overall survival rate of only 30% to 40% after 5 years. Results are more unfavorable in patients older than 60 years. 7,8 Immunotherapeutic approaches targeting TAAs to prevent relapse may represent a promising novel treatment option to improve the outcome of AML patients.Recently, in patients with AML, specific T-cell responses of cytotoxic T-lymphocytes (CTLs) were detected against the Wilms tumor gene WT1, proteinase 3 (PRTN3), and the receptor for hyaluronic acid-mediated motility (RHAMM; also known as CD168 or HMMR). 9-15 For these TAAs, clinical peptide vaccination trials have been initiated including patients with AML. 9,16,17 Furthermore, additional TAAs known to induce specific immune responses of CD8 ϩ T cells, such as PRAME, G250/CA9, BCL2, LAMR1, and hTERT, are also frequently expressed in AML. [18][19][20][21] While immunotherapy eliciting a specific T-cell response to TAAs expressed by leukemic ...

Taken together, the streptamer technology offers the advantage of selecting virus-specific CD8+ T cells at GMP level for adoptive T-cell transfer, thus inducing long-lasting specific CD8+ T-cell responses without increasing the risk for graft-versus-host disease.

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