Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

cific membrane antigen (PSMA) and prostatic acid phosphatase (PAP)] can also be
considered as TAAs. Mo-DCs used in conjunction with PSMA peptides have been
used in a phase II trial, which described one CR and 10 PRs amongst 37 patients
with presumed local recurrence [149]. There was a strong association between clinical
responders and pre-existing immune competence [151]. A protocol which uses
blood DCs and the novel DC-activating GM-CSF±PAP compound has been show to
generate T cell responses to PAP [157] and decreases in PSA levels as a tumor marker
stimulated a phase III study of patients with progressive metastatic disease.
Other cancers are also being addressed. Immune responses have resulted following
DC vaccination with carcinoembryonic antigen as RNA [118] or peptide [158]. Peptide-pulsed
DCs have now been reported to produce cytotoxic responses in breast
and ovarian cancer patients [159], and a single case report describes a clinical response
in breast cancer [160]. A single chronic myeloid leukemia patient produced
CTLs after DC vaccination [161]. DC vaccination with tumor lysates showed some
benefits in children with fibrosacroma [162].
Results in renal cell carcinoma appear to be promising, but perhaps more unexpected
have been the responses noted in patients with brain tumors [161, 163, 165].
However, as gliomas break the classic blood±brain barrier, the ability to deliver effector
T lymphocytes to this site is probably unimpaired.
What lessons have been learnt! As stated earlier, extensive immunological monitoring
to establish the surrogate markers is now mandatory. It appears that the immunosuppressed
patient with advanced cancer is not a good candidate for immunotherapy.
Other cautious conclusions may be drawn: immature Mo-DCs (lacking activation)
should not be used, the i.v. route may be less favorable and follow-up vaccination
may be essential (and an ethical obligation) in responding patients.
9.9
Phase III Clinical Trials
9.9 Phase III Clinical Trials
A phase III study in prostate cancer has been completed in patients with hormonerefractory
progressive metastatic prostatic cancer and is about to undergo its first
analysis [107]. A second phase III trial in hormone-sensitive patients is being initiated.
Further phase II studies are being explored prior to a phase III study on multiple
myeloma [107].
A phase III study performed by the Dermato-Oncology Working Group in melanoma
[111] will compare Mo-DC vaccination with melanoma peptides with conventional
treatment with dacarbazine. Other phase II studies are establishing protocols
which will encourage phase III studies. It is hoped that clinicians and scientists alike
will encourage and support these cooperative studies.
193