Rock1 Kiaa0053 Homer 3b

Other candidates targeted by T cells include MUC-1 and members of the MAGE family of genes. MUC-1 is an immunogenic epithelial mucin present in several solid tumors and has also been identified on malignant plasma cells.62 68 MUC-1-specific cytotoxic T-cell lymphocytes have been isolated in the bone marrow of patients with myeloma.6269 Vaccination trials in myeloma are underway, targeting the MUC-1 anti-gen.7071 Genes of the MAGE family are expressed in myeloma and anti-MAGE CTL clones are identified and were able to kill myeloma cell lines in vitro.63

Distinct populations of T cells may mediate GvHD and GvM. Specifically, clonal populations of T cells emerged in three of four patients after CD4+ DLI.72 The clones that were detected early after DLI correlated with GvM effect, while those clones appearing later were associated with the onset of GvHD. Interestingly, clones associated with GvM were often detectable prior to DLI and expanded up to 10-fold after DLI. In contrast, clones associated with GvHD were unde-tectable prior to DLI. These findings suggest that DLI may mediate GvM via an indirect effect on preexisting T-cell populations, while GvHD post-DLI is mediated by new T-cell populations that develop after DLI.

While much attention has focused on T cells, evidence is emerging that B cells and humoral immunity may also play an important role in the GvM effect. Animal studies have emphasized the importance of interactions between humoral responses and T-cell responses, both CD4+ and CD8+.73'74 Using SEREX, a technique in which the patient's serum is used to screen recombinant cDNA expression libraries, a large number of serologically defined tumor-associated antigens have been identified.75-78 Ten gene products have been identified in myeloma patients responding to CD4+ DLI using this tool.65 Two of the genes identified were also weakly recognized in a patient with chronic GvHD, perhaps suggesting a link between GvM and chronic GvHD. Two antigens identified, BCMA and ROCK-1, are highly expressed in primary myeloma cells as well as in myeloma cell lines, and further characterization of these myeloma antigens is being pursued to determine if they may serve as rational therapeutic targets.

0 0

Post a comment