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What's New In Research - December 22, 2003
Scientist reviews dendritic cell-based immunotherapy in multiple myeloma in a recent issue of the journal Leukemia and Lymphoma.
c) Copyright 2003 Cancer Weekly via NewsRx.com

According to published research from the United States, "Most patients with multiple myeloma (MM) cannot be cured with currently available therapies. Although complete remission could be achieved in about 50% of newly diagnosed patients with high-dose chemotherapy and tandem transplantation, relapses of the underlying disease occur frequently. To realize long-term disease-free survival, it will be necessary to develop complementary therapies that are non-cross-resistant with chemotherapy."

"To this end, immunotherapy aimed at inducing or enhancing tumor-specific immunity that may control or eradicate remaining tumor cells may be an appealing method," said Qing Yi at the University of Arkansas. "Dendritic cells (DCs) are professional antigen-presenting cells and considered the best natural adjuvants for immunotherapy in malignancies. Vaccination with tumor antigen-pulsed DCs has been shown to be protective and therapeutic in animal tumor models, and induced a strong tumor-specific immunity and durable tumor regression in human solid tumors and B-cell lymphoma. As a result, clinical trials in various human malignancies have been initiated."

"This review will focus on DC-based immunotherapy in multiple myeloma," stated Yi. "I will discuss myeloma antigens and antigen-specific immune responses, the capacity of DCs to present myeloma antigens and induce cytotoxic T-cell responses, and clinical experience of DC vaccination in myeloma patients."

Yi published the review in Leukemia and Lymphoma (Dendritic cell-based immunotherapy in multiple myeloma. Leuk Lymphoma, 2003;44(12):2031-2038).

Additional information can be obtained by contacting Qing Yi, Myeloma Institute for Research and Therapy, Arkansas Cancer Research Center, University of Arkansas for Medical Sciences, West Markham Street, Slot #776, Little Rock, AR 72205, USA. E-mail: YiQing@uams.edu.

Researchers say farnesyl transferase (FTase) inhibitors may be an effective treatment for of multiple myeloma.
(c) Copyright 2003 Cancer Weekly via NewsRx.com

According to recent research published in the journal Leukemia & Lymphoma, "Multiple myeloma is an incurable plasma cell malignancy in which Ras may be constitutively active either via interleukin-6 (IL-6) receptor signaling or by mutation.

"Inactivation of Ras may be achieved with FTase inhibitors a class of drugs which have shown promise in clinical trials particularly in patients with acute leukemia. This report investigates the efficacy of two distinct classes of FTase inhibitors in diverse myeloma cell lines and primary isolates," wrote D.M. Beaupre and colleagues, University of Miami School of Medicine.

"While Ras signaling has traditionally been linked to myeloma cell growth, we found that these compounds also potently triggered cell death. Death induced by perillic acid (PA) was caspase dependent without evidence of death receptor activation. Apoptosis was associated with mitochondrial membrane depolarization and activation of caspase-9 and 3 but proceeded despite over-expression of Bcl-X L, a known correlate of relapsed and chemorefractory myeloma," the researchers wrote.

"In addition, Fas ligand and TRAIL mediated apoptosis was potentiated in death receptor resistant (U266) and sensitive (RPMI 8226/S) cell lines. Of clinical relevance, the FTase inhibitor R115777 induced cell death in myeloma lines at doses observed in clinical trials," the researchers stated.

The researchers concluded: "Furthermore, both R115777 and PA induced cell death in primary isolates with relative specificity. Taken together these preclinical data provide evidence that FTase inhibitors may be an effective therapeutic modality for the treatment of multiple myeloma."

Beaupre and colleagues published their study in Leukemia & Lymphoma (Farnesyl transferase inhibitors enhance death receptor signals and induce apoptosis in multiple myeloma cells. Leuk Lymphoma, 2003;44(12):2123-2134).

For additional information, contact M.G. Lichtenheld, University of Miami, School of Medicine, Department of Medicine, Sylvester Cancer Center, Division Hematology & Oncology, RMSB 3014, 1600 NW 10th Avenue, Miami, FL 33136, USA.

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