Recognition of BCR-ABL positive leukemic blasts by human CD4(+)T cells elicited by primary in vitro immunization with a BCR-ABL breakpoint peptide

In chronic myeloid leukemia [CML] the classical 9;22 translocation results in a BCR-ABL fusion gene, which encodes chimeric BCR-ABL fusion 210 kD oncoproteins (p210(BCR-ABL)). The two main p210(BCR-ABL) fusion variants in CML, b2a2 and b3a2 are examples of well characterized antigens expressed by malignant cells. The possibility of an immunotherapeutic approach involving the fusion part of p210(BCR-ABL) in CML has previously been illustrated by observed peptide binding to major histocompatibility complex (MHC) class 1 alleles and by demonstrating the immunogenicity of p210(BCR-ABL) breakpoint peptides. In this report we show that in vitro immunization of human T cells with a 17 amino acid (aa) peptide representing the p210(BCR-ABL) fusion region resulted in peptide specific CD4(+) T-cell lines designated P4, P6, and P7. HLA DR4 (DRB1*0401) restricted T-cell line P4 and several subsequently derived clones recognized HLA-DRB1*0401 and p210(b3a2)-mRNA expressing blasts from an allogeneic patient with CML in blast crisis. Recognition appeared DR expression-dependent. No responses were observed with DR4 positive p210(BCR-ABL) negative cells or with p210(bBa2) leukemic cells with absent or insufficient expression of DR4. These observations indicate that oncoprotein p210(b3a2) can be degraded and processed for presentation by MHC class II molecules at the surface of leukemic cells. The SCR-ABL fusion region is in all likelihood presented as peptides by HLA DR and thus capable to act as a distinctive tumor antigen to peptide specific CD4(+) T cells. (C) 1996 by The American Society of Hematology.