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AUGUST 1999
VACCINE THERAPY
MUC1 tumor antigen. Peter Brossart and colleagues
utilized computer analysis of the amino acid sequence of the highly
immunogenic MUC1 tumor associated protein (type 1 transmembrane glycoprotein)
to identify two novel peptides with high binding probability to the HLA-A2
molecule. Cytotoxic T cells (CTL) were generated from healthy donors by
primary in vitro immunization using dendritic cells pulsed with the two novel
peptides. These peptide-induced CTLs lysed tumors expressing MUC1 in an
antigen-specific and HLA-A2-restricted fashion and the cytotoxic activity was
further increased by the addition of a T-helper epitope. This technique may
provide an approach for the development of vaccines that are broadly
applicable to many tumor-types. (Brossart P, et al. Blood 1999; 93:4309-4317)
HLA-MISMATCHED
HEMATOPOIETIC STEM CELL TRANSPLANTATION
Natural killer cell
alloreactivity.
Loredana Ruggeri et al. performed HLA compatibility serologic typing,
including an assessment of killer cell inhibitory receptor (KIR)
alloreactivity, on donors for 60 consecutive high-risk leukemia patients. All
pairs were haploidentical and 20 pairs were also KIR epitope incompatible
(donor vs. recipient) which predicted that donor natural killer (NK) cells
would cause GVH and GVL reactions. However, although NK cell clones of donor
origin killed allogeneic leukemia cells and lysed cryopreserved
pre-transplant recipient lymphocytes, no GVHD occurred and engraftment rates
were high. The data suggest that KIR epitope mismatching confers a potential
for engraftment and a GVL effect. (Ruggeri L, et al. Blood 1999; 94:333-339)
RENAL CELL CARCINOMA
(RCC)
Graft vs. Tumor (GVT)
effects: a case report. Richard Childs and coworkers reported the results of the treatment
of a patient with progressive metastatic RCC with a nonmyeloablative
allogeneic peripheral-blood stem cell transplant to exploit the GVT effect.
Serial PCR analysis of hematopoietic progenitors showed a mixed chimerism
which initially converted to 100% donor T-cells by day 60 and 100% donor
myeloid cells by day 100. Pulmonary metastases were no longer observable by
day 110 and a mild acute and chronic GVHD of the skin developed. This case
report suggests that exploiting GVT effects may be an effective treatment strategy
in patients with metastatic RCC. (Childs RW, et al. J Clin Oncol 1999;
17:2044-2049)
Cytokine therapy. Bernard Escudier and associates
conducted a randomized trial of interleukin-2 (IL-2; Chiron Therapeutics), or
interferon alfa-2a (IFNa2a; Roche), or combined IL-2 and IFNa2a in metastatic
RCC patients. Patients randomized to receive single-arm treatment (Il-2 alone
or IFNa 2a alone) were allowed to receive the other cytokine in a cross-over
trial when progression of disease developed (n=113). Only 4 partial responses
were observed and this cytokine crossover therapeutic approach was
ineffective in this RCC patient population. (Escudier B, et al. J Clin Oncol
1999; 17:2039-2043)
NON-HODGKIN'S
LYMPHOMA (NHL)
Rituximab efficacy in
bulky NHL. T.A.
Davis and colleagues conducted a phase II trial of single agent rituximab
(IDEC Pharmaceuticals Corp), a chimeric CD20 monoclonal antibody, in patients
with bulky relapsed/refractory low grade/follicular NHL (n=31). Rituximab was
administered intravenously (375 mg/m2) weekly x 4 doses. An overall response
rate of 43% was achieved with a median time to progression of 8.1 months
(range, 4.5 to 18.6 + months). The therapy was well tolerated and no patient
developed a human antichimeric antibody. Single-agent rituximab has clinical
activity in bulky progressive low grade/follicular NHL. (Davis TA, et al. J
Clin Oncol 1999; 17:1851-1857)
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