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MAY 1999
METASTATIC MELANOMA
Autologous melanoma
vaccine. Stanley
Leong and colleagues treated 20 stage IV melanoma patients with multiple
cycles of an autologous melanoma vaccine combined with an adjuvant injection
of BCG plus rhGM-CSF. Two patients had a CR and two patients had a PR with
regression of visceral and paraaortic masses. These objective responses
demonstrate that melanoma patients with large tumor burdens can respond to
specific immunotherapy. (Leong SPL, et al. J Immunother 1999; 22: 166-174)
MULTIPLE MYELOMA
Cytokine-based tumor
cell vaccine.
Alexander Shtil and associates generated potent granzyme B/
perforin-secreting (pore-forming) CTLs by immunizing mice with MPC11 cells (a
murine myeloma model) expressing GM-CSF and IL-12 or with MPC11
multidrug-resistant (MDR) variant cell lines transfected with GM-CSF/IL-12.
Immunization caused rejection of both transplanted MPC11 cells and the MDR
sublines in Balb/c mice even though these myeloma cells were resistant to
APO-1/CD95/Fas ligand. These data indicate that MDR mediated by mdr1/Pgp did
not prevent lysis by pore-forming CTLs and that this immunotherapy may be a
therapeutic approach for drug-resistant myeloma. (Shtil AA, et al. Blood
1999; 93: 1831-1837)
LEUKEMIA
Immunotherapy with ex
vivo-generated cytotoxic T lymphocytes (CTLs). Tuna Mutis and coworkers have
reproducibly generated CTLs specific for the hematopoietic cell-restricted
minor histocompatibility antigens (mHags) HA-1 and HA-2 from HA-1 and/or
HA-2-negative healthy blood donors using dendritic cells pulsed with HA-1 and
HA-2 synthetic peptides. These ex-vivo generated CTLs were found to
efficiently lyse leukemia cells (from AML and ALL patients) while
nonhematopoietic cells were unharmed. This study indicates that
ex-vivo-generated CTLs specific for hematopoietic mHags are a feasible therapy
for relapsed leukemia after allogeneic bone marrow transplantation and that
this therapy has a low risk of GVHD. (Mutis T, et al. Blood 1999; 93:
2336-2341)
GRAFT VS. TUMOR (GVT)
INDUCTION
Donor leukocyte
infusions (DLIs) as primary therapy. David Porter and associates treated 18 patients with
both hematologic and solid tumor malignancies with HLA-matched DLIs.
Interferon alfa-2b was administered to patients for a minimum of 4 weeks
prior to DLI therapy and patients without toxicity or donor leukocyte
engraftment were eligible to receive cytarabine or cyclophosphamide followed
by a second course of DLI treatments. In heavily pretreated patients, this
allogeneic adoptive immunotherapy caused a sustained chimerism, acute GVHD,
and a graft-vs.-tumor (GVT) response to occur which suggests that allogeneic
donor cell engraftment is necessary to induce a GVT reaction. (Porter DL, et
al. J Clin Oncol 1999; 17: 1234-1243)
CHRONIC LYMPHOCYTIC
LEUKEMIA (CLL)
CD40 activation of
CLL-B-cells.
Raymund Buhmann and colleagues induced B-CLL cells to become efficient
antigen-presenting cells by obtaining B-CLL cells from the peripheral blood
of CLL patients (CD40 was detectable in all B-CLLs) and culturing them on
CD40L expressing feeder cells. Stimulation of allogeneic T-cells with these
CD40-activated B-CLL cells resulted in the expansion of a specific CD8+ CTL
population while stimulation of autologous T cells resulted in the expansion
of CD4+ T-cell population that released interferon-g in response to the CD40-CLL
cells. These findings may be supportive of future immunotherapeutic
approaches to B-CLL. (Buhmann R, et al. Blood 1999; 93: 1992-2002)
NON-HODGKIN'S
LYMPHOMAS (NHL)
Response criteria. Bruce Cheson and coworkers
proposed standardized guidelines for response criteria for NHL clinical
trials developed during two meetings convened by international lymphoma
experts. The criteria include definitions of response and normal lymph node
size after treatment and a designation of a "complete response/unconfirmed"
category. In addition, with appropriate expertise the use of single-photon
emission computed tomography gallium scans are encouraged as a valuable
adjunct. It is anticipated that these guidelines will improve communication
and comparability among clinical trials. (Cheson BD, et al. J Clin Oncol
1999; 17: 1244-1253)
LUNG CANCER
NY-ESO-1 expression. Li Lee et al recently detected NY-ESO-1
expression, a gene in the class of cancer-testis antigens, in 11 of 16 small
cell lung cancer cell lines and 3 of 7 NSCLC cell lines by reverse
transcriptase and PCR amplification techniques. They also found that lung
cancer cells expressing NY-ESO-1 are recognized by an HLA-restricted
cytotoxic T-cell clone and that NY-ESO-1 expression is induced by the
demethylating agent, 5-aza-2¢-deoxycytidine. These results suggest that
NY-ESO-1 may be a potential target for lung cancer immunotherapy. (Lee L, et
al. Cancer J Sci Am 1999; 5: 20-25)
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