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

11.4HCV
tive tumor responses, while in five other patients, stable disease was induced after
previous progression. Interestingly, stable disease was maintained under repeated
booster injections for more than 2 years in some of the patients. Some of these patients
remained in stable disease with periodic HCVs for more than 2 years. Antitumor
immune responses were seen only in patients who still had the capacity to
mount delayed-type hypersensitivity responses to at least one of a set of common recall
antigens. As evidenced by histological analyses of tumor lesions that became inflamed
after vaccinations, the vaccination induced or mediated T cell relocation into
tumor nodules [171].
The first study with HCV using allogeneic DCs and autologous tumor cells was completed
with 17 patients with metastatic renal cell carcinoma [151]. HLA-A2-restricted
cytotoxic T cells reactive with the Muc1 TAA were shown to be induced and it could
be demonstrated that CD8 + T lymphocytes were recruited into tumor challenge sites.
Again, side effects were minor. There were four complete and two partial responses,
and one patient had a mixed response, indicating that this approach might be safe
and effective in patients with renal cell carcinoma.
Avery interesting report was recently published of a first HCV trial with eight patients
with glioma [153]. Two of these patients experienced partial responses. No serious adverse
effects were observed in any of the patients, whereas most of the patients
showed signs of changes in their immune status as evidenced by increased lymphocyte
counts and enhanced IFN levels in the peripheral blood. Three of the four clinical
HCV trials which have yielded cases of objective clinical responses, i. e. complete responses
or reduction of the tumor mass by 50 %, have used hybrids of autologous tumor
cells with allogeneic APCs, activated B cells or DCs. These initial observations
might indicate that the T cell response against the allogeneic MHC molecules indeed
provides additional co-stimulatory support for the tumor-specific Tcell responses.
So far, renal cell carcinoma patients seem to benefit more often than melanoma patients
from a HCV therapy [151, 171±173]. The number of patients treated in the
glioma trial is too low to support any conclusions in this direction [153]. Both tumors,
renal cell carcinoma and melanoma, are considered to be relatively immunogenic
tumors whereby the known melanoma-associated antigens by far outnumber
the antigens associated with renal cell carcinoma [38]. The difference in clinical responses
seen in the HCV trials might reflect a difference in antigenicity, but more
likely is related to the biology of these tumors, with malignant melanoma being considered
more aggressive, or to the treatments received by the patients before the vaccination
therapy. Whereas the majority of the melanoma patients in the clinical vaccination
trials had received chemotherapy before, this was the case only for a few exceptional
patients with renal cell carcinoma. In addition to the general immune suppression
often associated with chemotherapy, a recent report demonstrated that chemotherapy
can selectively eliminate tumor-specific T cells from the circulation of the
patients [26]. Chemotherapy is certainly incompatible with specific vaccination therapy
and these two regiments are not combined. However, so far there is no information
available as to the extent to which the cellular immune response capacity of patients
can recover after chemotherapy, i.e. if a complete or at least sufficient recovery
is possible; there is also information lacking regarding the kinetics of this process.
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