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BioOncology Watch Timely Information for Practicing
Physicians |
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NOVEBMER 2000 Hepatocellular Carcinoma (HCC) Adoptive
immunotherapy. Tadatoshi Takayama and colleagues
conducted a study in which patients who had undergone curative surgical
resection for HCC were randomized to receive infusions of activated
autologous lymphocytes or no adjuvant treatment (n=150). Mononuclear cells were obtained from a
peripheral blood sample (50 mL) drawn prior to surgery and were cultured with
interleukin-2 and immobilized anti-CD3 monoclonal antibody. A 1,400-fold T-cell expansion was achieved
with this culture system. The
activated lymphocytes were re-infused into the patient at weeks 2, 3, 4, 12,
and 24 after surgery. After a median
follow-up of 4.4 years (range, 0.2 to 6.7 years), the median time to first
recurrence was 2.8 years for the immunotherapy group versus 1.6 years for the
control group (p=.008). The
immunotherapy patients had longer recurrence-free survival (p=.01) and a
trend towards improved overall survival (p=.09) compared to control
patients. These results show that
adjuvant adoptive immunotherapy can improve clinical outcomes for patients
with HCC. (Takayama T, et al. Lancet
2000;356:802-807) Hematologic Malignancies
Donor lymphocyte
infusions (DLI) for chronic myeloid leukemia (CML).
Francesco Dazzi et al report the results of DLI treatment for 66
consecutive patients with BCR-ABL-positive CML who had relapsed after
allogeneic stem cell transplantation (SCT).
Forty-four patients (67%) achieved a molecular remission following
DLI. Relapse to advanced phase
disease and an interval between transplant and relapse of <9 months were found
to be poor prognostic factors for response.
After a median follow-up of 29 months, only 4 patients have reverted
to a PCR-positive status. The 3-year
survival for patients who had a molecular remission was 95% compared to 53%
for those who did not have a molecular remission (p=.0001). This study indicates that DLI therapy may
frequently result in durable remissions for patients with CML who relapse
following SCT. (Dazzi F, et al. Blood
2000;96:2712-1716) In vivo CAMPATH-1H for graft-versus-host disease
(GVHD) prevention. Treatment-related mortality is a major
obstacle to successful allogeneic SCT.
Nonmyeloablative purine analogue conditioning has decreased
regimen-related mortality, however the incidence of significant (grade 2-4)
GVHD remains high (38% to 60%).
Panagiotis Kottaridis and coworkers included CAMPATH-1H, a humanized
anti-CD52 monoclonal antibody that induces T-cell lysis, as a component of a
nonmyeloablative conditioning regimen for 44 patients with a variety of
hematologic malignancies. Patients
also received GVHD prophylaxis with cyclosporine alone (n=38) or cyclosporine
plus methotrexate (n=6). At a median
follow-up of 9 months (range, 3 to 29 months), 33 patients remained in
complete remission. There were no
cases of grade 3 or 4 acute GVHD reported and only 1 patient developed
chronic GVHD. The nonrelapse-related
mortality was 11%. Longer follow-up
is required, but these data suggest that the addition of CAMPATH-1H to a
nonmyeloablative conditioning regimen decreases the incidence of GVHD without
jeopardizing engraftment durability.
(Kottaridis P, et al. Blood 2000;96:2419-2425) Immune
recognition of myeloma cells. The monoclonal immunoglobulin
secreted by myeloma cells can serve as a tumor specific antigen because of
the unique structure of its variable region (idiotype). Yiwen Li and associates immunized 2
healthy stem cell donors with idiotype protein obtained from their recipients
with multiple myeloma. T-cells from
the immunized donors were found to release high levels of T-helper 1-type
cytokines in response to stimulation with myeloma cells from their
recipients. In addition, they were
also able to generate cytotoxic T-lymphocytes (by means of in vitro stimulation with autologous
dendritic cells pulsed with idiotype protein), which lysed myeloma cells
specifically. These experiments
demonstrate that myeloma cells can serve as immune targets of an
idiotype-induced T-cell response. (Li
Y, et al. Blood 2000;96:2828-2833) Breast Cancer
An anti-HER2 monoclonal antibody (MAb) and
geldanamycin (GA) immunoconjugate. GA is a cytotoxic antibiotic that inhibits HER2
activity. Thus, Raya Mandler et al
attempted to enhance the inhibitory activity of anti-HER2 MAb by coupling it
to GA. Low concentrations of the
immunoconjugate were observed to inhibit the proliferation of
HER2-overexpressing cell lines. The
50% inhibitory concentration for the GA-coupled anti-HER2 MAb was 40 mg/mL compared to 1,650 mg/mL for the anti-HER2 MAb alone. In addition, GA
alone reduced HER2 levels by only 20% and the GA-coupled anti-HER2 MAb did
not inhibit the proliferation of HER2-negative cell lines. These findings suggest that GA
immunoconjugates represent a potentially effective means of target-directed
anticancer immunotherapy. (Mandler R, et al. J Natl Cancer Inst 2000;
92:1573-1581) |
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