mRNA expression of tumor associated antigens in patients with chronic lymphocytic leukemia

Abstract

Specific immunotherapy might be a novel option for therapy of patients with B-cell chronic lymphocytic leukemia (B-CLL).To define potential target antigens, we screened the mRNA expression of twelve tumor/leukemia associated antigens (TAA/LAAs) from the literature: fibromodulin, survivin, oncofetal antigen-immature laminin receptor protein (OFA-iLRP), B-melanoma antigen (BAGE), the carboanhydrase 9 (CA9/G250), melanoma antigen (MAGE1), the preferentially expressed antigen in melanoma (PRAME), proteinase, Syntaxin, human telomerase catalytic subunit (hTERT) and the Wilms tumor gene 1 (WT1), the renal cell cancer antigen NY-Ren60, as well as six LAAs defined previously by serological analysis of recombinant cDNA expression libraries of myeloid leukemias patients: the receptor for hyaluronic acid mediated motility (RHAMM/CD168), the M-phase phosphoprotein 11 (MPP11), the particularly interesting new Cys-His protein (PINCH), the heat shock protein (HSJ2), the myc-associated zinc-finger protein (MAZ). Peripheral blood mononuclear cells from 30 B-CLL patients and 20 healthy volunteers (HVs) were evaluated by conventional and quantitative RT-PCR. mRNA of RHAMM, fibromodulin, syntaxin and NY-Ren60 was expressed in 55 - 90 % and of HSJ2, MAZ and OFA-iLRP in 90 - 100 % of the patients. Only RHAMM, fibromodulin, PRAME and MPP11 showed expression in B-CLL patients, but not in HVs. RHAMM mRNA expression was significantly higher in B-CLL patients than in HVs. Specific cytotoxic T lymphocyte responses in B-CLL patients against RHAMM/CD168 were measured in vitro. In mixed lymphocyte peptide cultures, RHAMM specific responses by CD8+HLA-A2/R3tetramer+CCR7-CD45RA high effector T-cells were detected. We conclude that RHAMM/CD168 might be an interesting target for future immunotherapies in B-CLL patients.