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JANUARY 1999
DENDRITIC CELL (DC)
FUNCTION AND DEVELOPMENT
Effects of FLT3-ligand
(FL) administration.
Jean-Marie Peron et al and Peter Brossart et al recently investigated the
effects of FL on DC function and development because of previous reports that
FL administration increases the accumulation of DCs in tissues. Peron et al
studied a murine liver metastasis model (C57BL/6 mice injected with C3
sarcoma cells) and found FL treatments were associated with an enhancement of
DCs in the liver and a reduction of the number of hepatic metastases compared
to control animals (P<0.05). Brossart et al observed that the induction of
the development of DCs from peripheral blood mononuclear cells in culture
requires the presence of IL-4 in addition to FL. They also showed that CD40
ligation alone promotes blood monocyte differentiation into functional DCs.
These studies support the development of clinical studies to evaluate
cytokine-induced immunotherapy and demonstrate that blood monocytes are an
additional source of DCs. (Peron J-M, et al. J Immunol 1998; 161: 6164-6170
and Brossart P, et al. Blood 1998; 92: 4238-4247)
GRAFT-VERSUS-HOST
DISEASE (GVHD)
Monoclonal antibody
(MoAb) therapy.
Donna Przepiorka and colleagues conducted a phase II clinical study of
BIT-322 therapy (a monoclonal anti-human CD2 rat antibody; BioTransplant,
Inc) in 20 transplant recipients with steroid-resistant GVHD. This therapy
resulted in a 55% response rate (6 complete responders and 5 with a reduction
in GVHD grade) and was associated with little toxicity. In addition, Bruce
Blazar et al recently studied the effects of the CD2: CD48 pathway on GVHD in
murine models of bone marrow transplantation (BMT). They found T-cell
mediated GVHD was inhibited by anti-CD2 + 48 MoAb infusions, but that these
MoAb infusions, (primarily anti-CD48) inhibited alloengraftment and delayed
hematopoietic recovery. These studies demonstrated that antibodies targeting
CD2 may be effective therapy for acute GVHD but should be used with caution
because CD48 has a critical role in regulating post-BMT hematopietic
recovery. (Przepiorka D, et al. Blood 1998; 92: 4066-4071 and Blazar BR, et
al. Blood 1998; 92: 4453-4463)
MONOCLONAL ANTIBODY
(MOAB) THERAPY FOR NON-HODGKIN'S LYMPHOMA (NHL)
Rituximab (an anti-CD20
MoAb) pharmacokinetics. Rituximab (IDEC Pharmaceuticals Corp.) has been shown to have
activity in low grade NHL. N.L. Berinstein and coworkers describe the
pharmacokinetic data obtained from 166 NHL patients treated with rituximab (4
weekly infusions) in phase III studies. They found the rituximab half-life
and serum levels to increase from after the 1st infusion to after the 4th
infusion. Also, the median serum level of rituximab was higher in responders
than non-responders and lower rituximab serum levels were associated with bulky
disease and IWF histologic type A disease. The authors suggest that the
rituximab half-life increases as CD20+ B cells are cleared and subsets of
patients may benefit from higher doses of rituximab. (Berinstein NL, et al.
Ann Oncol 1998; 9: 995-1001)
INTERFERON ALFA
THERAPY
Colon carcinoma. Norman Wolmark and colleagues
report the results of NSABP protocol C-05 in which 2,176 patients with Duke's
stage B or C colon cancer were randomized to receive 5-fluorouracil +
leucovorin with or without interferon alfa-2a (IFN). Patients were stratified
by sex, stage, and number of involved nodes. The addition of IFN was found to
confer no benefit: At 4 years of follow-up there was no difference in
disease-free survival or overall survival between the two treatment groups.
(Wolmark N, et al. J Natl Cancer Inst 1998; 90: 1810-1816)
Chronic myelogenous leukemia (CML). Jorge Cortes and coworkers
studied 90 Philadelphia chromosome (Ph) - positive CML patients who had
undergone cytogenetic clonal evolution (the presence of karyotypic
abnormalities in addition to the Ph) and had received interferon alfa
(IFN-a)-based therapy. The IFN-a treatments completely suppressed cytogenetic
clonal evolution in 41 patients (46%). The median survival for these patients
was greater than those patients with no response or less than complete
suppression (66 vs. 30 months; P=0.01). The authors concluded CML patients
with cytogenetic clonal evolution can respond to IFN-a therapy and a complete
response is associated with longer survival. (Cortes J, et al. J Clin Oncol
1998; 16: 3279-3285)
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