Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Cytokine-depot tumor vaccines: Basic principles

FW Falkenberg PhD, OC Krup PhD, M Peters MSc, C Desel MSc, U Falkenberg PhD, R Schröder MSc, I Kroll MSc, G Böse MSc, A Brockmann MSc, A Schulte MSc, B Schoengen MSc, K Zinkant MSc

Ruhr-Universityät Bochum, Abteilung für Medizinische Mikrobiologie, Bochum, Germany,

AIMS: The use of cytokine gene-transfected tumor cells as tumor vaccines has introduced a completely novel concept into tumor therapy. In an attempt to mimic this approach we have applied irradiated tumor cells mixed with cytokine-loaded depot particles as tumor vaccines. This approach has the advantage that the composition of the vaccine (tumor cell dose, cytokine dose) as well as the vaccination conditions (vaccination site, vaccination course) can be elaborated on a scientific and quantitative base rather than by trial and error. METHODS: In order to investigate the feasibility of the approach, prophylactic (vaccination prior to a challenge with a lethal dose of vital tumor cells) and therapeutic (vaccination after tumor induction with a lethal dose of live tumor cells) vaccination experiments were done. Most of the work reported here has been done with rhuIL-2 encapsulated in liposomes or adsorbed to aluminum hydroxide. RESULTS: Using vaccines consisting of irradiated tumor cells mixed with IL-2 in depot form (cytokine-depot-tumor-vaccines) we were able to protect mice from a tumor challenge by prophylactic vaccination. Moreover, it was also possible to cure tumor-bearing mice from existing tumor disease. The results obtained with a variety of cytokines, depot formulations, and with several murine model tumors indicate that this is a generally applicable approach. CONCLUSIONS: The results obtained show that IL-2-depot formulations can serve as very effective adjuvants for tumor vaccines. Due to the easiness of preparation and handling cytokine-depot-tumor-vaccines have many advantages over tumor vaccines consisting of cytokine gene-transfected tumor cells.

KEY WORDS: interleukin-2.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on immunotherapy.