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Immunotherapies and Control Of Residual Disease
By Brian G.M. Durie, MD
07.14.01

INTRODUCTION

Dr. Douglas Joshua, of the Royal Prince Albert Hospital in Australia, chaired this session. Four speakers presented, two dealing with the new immune therapy target antigens hTERT and TRAIL and two with new methods to purge stem cells as a part of high-dose chemotherapy with stem cell transplantation.

HIGHLIGHTS

Dr. Joachim Schultze of the Dana Farber Cancer Institute discussed the significance of the hTERT antigen, the catalytic subunit of telemerase and enzyme that is present on the surface of 85% of cancer cells including myeloma. hTERT confers "immortality" to growing malignant cells. The aim is to trigger immune T lymphocytes from myeloma patients to react selectively against this surface hTERT protein and thereby inhibit the immortality potential of actively growing myeloma cells. The method is to develop a panel of suitable surface antigens that will function as a sufficiently strong trigger to produce an effective immune response. This work is in its early stages.

The second presentation was by Dr. Steve Treon, also from Dana Farber, who discussed his recent studies with TRAIL (TNF-related apoptosis-inducing ligand). Myeloma cells have surface receptors for TRAIL. Administration of synthetic TRAIL (produced by recombinant genetic engineering) causes myeloma cells to undergo cell death, or apoptosis. Other agents that affect signal-transduction pathways, such as the new proteasome inhibitor PS-341, an NFkB inhibitor, enhance this induction of cell death. Again, these studies are in the early stages, and patient trials (with TRAIL) will be awaited with interest.

Dr. Andrew Belch of the University of Alberta in Canada presented results of studies on novel strategies to purge stem cells being used for stem cell transplantation. He focused on the use of SLT-1 (shiga-like– toxin), a bacterial toxin produced by certain strains of Eschericia coli that can infect the gastrointestinal tract. SLT-1 can destroy myeloma cells in vitro while sparing normal bone marrow stem cells. Testing of SLT-1 in transplant patients is just beginning.

The final presentation was by Dr. Mitterer from Italy. He and his colleague, Dr. Straka of Ludwig Maximillians University in Germany, used monoclonal antibodies against B lymphocytes (presumed myeloma precursor cells) to clear stem cell preparations of residual contaminating myeloma precursor cells. Effects in 55 patients were compared with those in 57 patients in whom no purging was performed. Preliminary data indicate that both length of remission and overall survival are improved with use of this technique. Further follow-up is required, and additional studies are planned. It should be noted that overall, purging still needs to be established as a useful technology. Results thus far from different international groups have been conflicting. Although purging definitely yields a "cleaner" stem cell product, it is not so clear to what extent remission and survival are impacted.


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