Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches.
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 T-cell 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.
Greiner
Jochen
J
Department of Internal Medicine III, University of Ulm, Robert-Koch-Str.8, 89081 Ulm, Germany. jochen.greiner@uniklinik-ulm.de
Schmitt
Michael
M
Li
Li
L
Giannopoulos
Krzysztof
K
Bosch
Katrin
K
Schmitt
Anita
A
Dohner
Konstanze
K
Schlenk
Richard F
RF
Pollack
Jonathan R
JR
Dohner
Hartmut
H
Bullinger
Lars
L
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D019556:COS Cells; D002522:Chlorocebus aethiops; D018572:Disease-Free Survival; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000235:genetics* / Q000276:immunology; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics / Q000276:immunology; D015996:Survival Rate
D000951:Antigens, Neoplasm; D000939:Epitopes; D010455:Peptides; D012334:RNA, Neoplasm