Adoptive Immunotherapy

Data demonstrate that DLI mediates a significant GvM effect, and this offers the potential to effectively and selectively treat MRD after transplantation.3840 Defining the role and timing of DLI after nonmyeloab-lative transplantation is currently underway. Efforts to identify the mediators of GvM and their target antigens are in progress, and hopefully it will be possible to expand antigen-specific DLI ex vivo to treat patients while at the same time reducing the complications related to GvHD.

Strategies are also available for increasing the antigen-presenting capacity of myeloma cells and their ability to stimulate donor T cells targeting myeloma. CD40 activation of myeloma cells upregulates Class I and Class II HLA and costimulatory molecules,79 and CD40-activated myeloma cells trigger a brisk allogeneic, as well as autologous, T-cell response.80'81 In preclinical studies, histocompatible donor cells can be expanded ex vivo using CD40-activated patient myeloma cells as stimuli.

Another strategy for ex vivo expansion of T cells for adoptive immunotherapy is directed toward a novel, widely expressed tumor antigen derived from the telomerase catalytic subunit (hTERT).64 hTERT is a ribonucleoprotein expressed in high levels in more than 85% of human cancers, including multiple myeloma, but is expressed in few normal tissues. In preliminary studies using donor cells, this expansion strategy has been used to generate MHC Class I restricted CTL that are specific for an hTERT peptide and kill hTERT-bearing myeloma cells. These studies will establish the conditions for testing the efficacy and safety of allogeneic, as well as autologous, hTERT CTL immunotherapy, and may provide the framework for a subsequent clinical treatment protocol in myeloma.

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