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APRIL 1999
MALIGNANT GLIOMA
Retroviral delivery of
interleukin-4 (IL-4). IL-4 has previously been shown in preclinical studies to mediate
tumoricidal activity by eliciting an initial immune response and by
inhibiting tumor angiogenesis. Mary Saleh et al investigated the
effectiveness of IL-4 treatment of gliomas by inserting ecotropic retrovirus
packaging cells that were transfected with a retroviral vector encoding mouse
IL-4 into C6 cell glioma tumors that had been either subcutaneously implanted
in athymic nude mice or had been stereotactically implanted intracranially in
immunocompetent Wistar rats. This therapy resulted in tumor growth arrest in
the mouse model and in histologically proven eradication of the gliomas in
the rat intracranial model. While these results in animal models may not
translate to clinical effectiveness in humans, these data do show that C6
gliomas in immunocompetent rats are eradicated by the insertion of cells
producing IL-4 retrovirus. (Saleh M, et al. J Natl Cancer Inst 1999; 91:
438-445)
MULTIPLE MYELOMA (MM)
Muc-1 core protein
expression. Muc-1
is an epithelial antigen that has been found to be expressed on MM cells.
Steven Treon and colleagues utilized monoclonal antibodies to Muc-1 core
protein determinants to investigate if Muc-1 is a suitable target for
immunotherapy in MM patients. MM cell lines, MM patient plasma cells, MM
patient B cells, and normal circulating B cells were found to express Muc-1
core protein by flow cytometry analysis. In contrast, Muc-1 core protein was
absent on splenic and tonsillar B cells, CD34+ stem cells, T-cells, normal
bone marrow plasma cells, and 28 of 32 non- MM neoplastic cell lines tested.
Furthermore, dexamethasone induced an upregulation of Muc-1 expression on MM
cell lines at concentrations that are readily achieved clinically. These data
provide a rationale to target the Muc-1 core protein as immunotherapy for MM.
(Treon SP, et al. Blood 1999; 93: 1287-1298)
Dendritic cells (DC). Noopur Raje and coworkers
determined that the yield, pattern of antigen expression, and function (mixed
lymphocytic reaction) of DCs from MM patients were equivalent to that of DCs
from normal donors. No functional differences were noted between peripheral
blood (PB) DCs and bone marrow (BM) DCs. Because recent studies have reported
the presence of Kaposi's sarcoma herpes virus (KSHV) gene sequences in BMDCs
in MM, nested PCR testing for KSHV gene sequences was done and was positive
in 16/18 MM BMDCs and only 1/5 MM PBDCs. This study shows that MM DCs remain
functional despite detection of KSHV gene sequences. Additionally, PBDCs are
as effective as BMDCs and have a lower rate of KSHV gene sequence detection.
Thus, the PB is an attractive source for DCs for immunotherapeutic approaches
to treatment. (Raje N, et al. Blood 1999; 93: 1487-1495)
RITUXIMAB THERAPY
(ANTI-CD20 CHIMERIC ANTIBODY)
Infusion-related side
effects. Dr. John
Byrd and colleagues describe a new clinical adverse event in 5 patients with
hematologic malignancies (prolymphocytic leukemia [n=2], CLL [n=2],
transformed NHL [n=1]) who were treated with rituximab. Each patient
presented with a high number of circulating tumor cells in the peripheral
blood and had bulky adenopathy or organomegaly. Rituximab therapy resulted in
rapid tumor clearance from the circulation and was associated with severe
first infusion-related toxicity characterized by fever, rigors, bronchospasm,
and thrombocytopenia as well as evidence of a mild tumor lysis syndrome. This
symptom complex was self-limiting and four patients were subsequently treated
with rituximab. Patients who have a high number of circulating tumor cells
have an increased likelihood of developing severe infusion-related reactions
with rituximab therapy. Although rituximab is approved for use only in
relapsed low-grade NHL, these data also suggest rituximab activity in other
lymphoid neoplasms. (Byrd JC, et al. J Clin Oncol 1999, 17: 791-795)
METASTATIC
MELANOMA
Combination
chemoimmunotherapy.
Steven Rosenberg and associates conducted a trial in which 102 metastatic
melanoma patients were prospectively randomized to receive chemotherapy
(cisplatin, dacarbazine, and tamoxifen) alone (52 patients) or chemotherapy
followed by interferon alfa-2b and interleukin-2 therapy (50 patients). The
response rates were 27% and 44% (P=0.071) for the chemotherapy alone and
chemoimmunotherapy groups, respectively. However, there was a trend toward a
survival advantage in the chemotherapy alone group (15.8 vs 10.7 months;
P=0.052). Moreover, treatment-related toxicity was greater in the
chemoimmunotherapy patients. Thus, immunotherapy increased toxicity in this
trial and did not increase survival. However, it should be noted that many
chemoimmunotherapy patients did not receive optimal treatment doses due to
toxicity). (Rosenberg SA, et al. J Clin Oncol 1999; 17: 968-975)
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