The Receptor for Hyaluronic Acid Mediated Motility (RHAMM/CD168) Is a Potential Target for Immunotherapy of Patients with B-Cell Chronic Lymphocytic Leukemia.

Definition of appropriate target antigens might open new avenues to antigen targeted immunotherapies for patients with B-cell chronic lymphocytic leukemia (B-CLL). We screened the mRNA expression of tumor associated antigens (TAAs), from the literature (fibromodulin, survivin, OFA-iLRP, BAGE, G250, MAGE1, PRAME, proteinase, Syntaxin, hTERT, WT-1), and TAAs defined earlier by serological analysis of cDNA expression libraries from leukemic cells (PINCH, HSJ2, MAZ, MPP11, RHAMM/CD168, NY-Ren60). Peripheral blood mononuclear cells from 43 B-CLL patients and 20 healthy volunteers (HVs) were examined by conventional and quantitative RT-PCR. mRNA of RHAMM/CD168, fibromodulin, syntaxin and NY-Ren60 was expressed in 55–90%, mRNA of HSJ2, MAZ and OFA-iLRP in 90–100% of the patients. No expression of WT-1, h-TERT, BAGE, G250, MAGE1 and survivin was observed. Low (2–20%) expression frequencies of MPP11, PINCH, PRAME and proteinase were detected. RHAMM/CD168, fibromodulin, PRAME and MPP11 showed expression in B-CLL patients, but not in HVs. Because of the exquisite tissue expression of RHAMM/CD168 and its high expression frequency in B-CLL patients even in early stages of disease, mixed lymphocyte peptide culture (MLPC), enzyme-linked immunosorbent spot (ELISPOT) and flow cytometry were performed for antigen specific T cells. In MLPC, RHAMM specific responses by CD8+HLA-A2/R3tetramer+CCR7-CD45RAhigh effector T cells were detected. Moreover, we observed an enhanced RHAMM/CD168 specific CD8+ T cell response after vaccination in one from four HLA-A2 positive B-CLL patients vaccinated with tumor cell lysate pulsed dendritic cells. Therefore, RHAMM/CD168 is an interesting candidate antigen for future immunotherapies in both ZAP-70 (+) and ZAP-70 (−) B-CLL patients.