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

healthy individuals might thus have the additional advantage of being an unrestricted
source of competent immune stimulatory cells [164, 165].
In summary, the HCV approach was designed:
. To utilize a large variety of usually unidentified TAAs.
. To provide co-stimulating signals.
. To recruit and activate Tcell help for the induction of tumor specific cytotoxic Tcells.
Classical hybridoma technology aims at long-term lines that are selected on the basis
of, primarily, their resistance to cytostatic drugs and, subsequently, according to the
specific functionality desired. Usually, both fusion partners cells are of the same tissue
origin and are controlled by very similar genetic programs. One of the fusion
partners is a tumor cell selected for good growth properties. The hybrid cells needed
for cancer immune therapy are very different [35]. First, the fusion partners are
usually heterogeneous, i. e. they are of very different tissue origin controlled by different
genetic programs, and, second, the tumor cell has in most cases not been
adapted for stable growth in culture. On the other hand, long-term survival and
growth of the hybrid cell is not required for the vaccination effect. Just the opposite ±
it must be ensured that the hybrid cells cannot survive and proliferate after injection
into the patient. The vaccines are irradiated prior to inoculation to prevent tumor
spreading in the vaccinee.
Since usually the hybrid cells cannot be expanded, the fusion technology must be designed
to yield high fusion efficiencies independent of the specific types of cells
used for hybridization. Electrofusion is one of the options for this purpose as it has a
relatively high efficiency of hybrid cell generation and is relatively independent of
the cell types that shall be fused [166, 167]. As the exact fusion conditions are defined
by the setting of the electrical parameter of the power suppliers and pulsers, this
technique is well reproducible.
11.4.2
HCV in Preclinical Studies
11.4HCV
The HCV concept has been tested successfully in a number of different animal tumor
models including intradermal thymoma [161], liver cell and other carcinomas
[149, 154, 156, 159, 162, 168], brain tumors such as neuroblastoma [152, 155], melanoma
[169], and hematological cancers [170]. The fusion partners in the earlier
works were B lymphoma cells; in the recent reports, DCs. Therapeutic vaccinations
as well as primary immunizations with the hybrid cells were tested in the very first
experiments [161, 162]. In all cases eradication of established tumors and induction
of specific long-lasting antitumor immunity was induced by a single injection of the
vaccine. The thymoma [161] study provided evidence of the need for cell hybridization,
i.e. only the fused tumor and APCs induced tumor rejection and antitumor immunity,
but not the parental cells mock-fused to themselves, or mixtures of these
mock-fused cells. It could also be demonstrated that helper T cells specific for the allogeneic
MHC are involved in the induction of the immune response. The eradica-
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