Stem Cells, Vol 11, 144-153, Copyright © 1993 by AlphaMed Press
Practical aspects of cytokine therapy
H Zwierzina
Medizinische Universitatsklinik Innsbruck, Austria.
Biological therapy with cytokines and growth factors represents a
completely new approach in cancer therapy and forces us to adapt our
research procedures originally tailored to cytotoxic agents. The lack of
reliable predictive in vitro systems or animal models for biological agents
and the fact that promising candidates must proceed rapidly to the clinic
implies that a drug's therapeutic potential can only be assessed following
careful studies in man. Consequently, the effectiveness of clinical trials
must be improved by closely relating them to research programs utilizing
material from cytokine-treated patients. In clinical practice, patients
with low tumor burden may profit most from therapy with immunomodulators,
which requires minimally effective doses rather than maximally tolerated
dosages. Hemopoiesis can be influenced either by hemopoietic growth factors
or by negative regulators, which may prevent stem cell damage during
chemotherapy. According to the principles of autocrine growth mechanisms,
resting malignant cells may be triggered into cell cycle by their growth
factor(s), thus becoming more sensitive to chemotherapy. When discussing
the fascinating aspects of the cytokine network, we must be aware that we
are only beginning to understand the mechanisms of biological therapy and
that close cooperation among preclinical and clinical scientists is
required for its rational development.
