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

342 16 Immunocytokines: Versatile Molecules for Biotherapy of Malignant Disease
growing primary tumors and one spontaneously metastasizing tumor [115]Ç These
data indicated such a vascular targeting approach to be effective in clinically relevant
tumor models. Importantly, the antitumor effect of targeting the tumor vasculature
was amplified by a simultaneous attack on the tumor compartment, which was effective
against both primary tumors and spontaneous metastases [115]. In fact, the simultaneous
targeting of the vascular and tumor compartments proved very effective,
since it combined a decrease in tumor cell nourishment with the active destruction
of tumor cells, leading to a regression of primary tumors and the eradication of distant
metastases. This finding was in contrast to a single vascular compartment-directed
approach using two different anti-angiogenic treatment strategies that resulted
only in suppression of s.c. tumor growth in a syngeneic model [116]. In contrast, in
our strategy, the tumor compartment-specific response was mediated by inflammatory
cells that were activated and directed to the tumor microenvironment by the tumor-specific
immunocytokines. Significantly, the anti-angiogenic strategy, although
quite effective in growth suppression of primary tumors with a well-established vascular
supply, lacked a similar efficacy against distant micrometastases when used as
monotherapy. However, in such a minimal residual disease setting with small tumor
loads characterized by poor vascularization, the antitumor compartment treatment
arm used in our combination therapies was quite effective when used as monotherapy
[11, 92]Ç In this situation, the role of anti-angiogenic treatment strategies could
be to suppress micrometastasis-induced neovascularization and subsequent enlargement
of metastatic foci [111]. This, in turn, would facilitate eradication of such micrometastases
by tumor compartment-directed therapies, which are optimally effective
in the minimal residual disease setting.
16.7
Conclusions and Perspectives
The effective adjuvant treatment of solid tumors remains a major challenge in clinical
oncology. Although, a variety of novel therapeutic strategies have became available
for biotherapeutic treatment, most of these were evaluated as monotherapies
and often resulted in diminished enthusiasm due to poor clinical response rates. In
view of the increased success of cancer chemotherapy due to sophisticated combination
of drugs with distinct modes of action, a similar approach may be called for in
the adjuvant treatment of cancer. Consequently, the preclinical evaluation of the presence
or absence of synergystic effects in the combined adjuvant treatment strategies
described in this chapter may aid in providing the critical information necessary to
design successful adjuvant treatments for cancer. Such efforts combined with rapid
clinical evaluations may provide the key to markedly advance cancer therapy in the
21st century.