[Frontiers in Bioscience 16, 2233-2242, June 1, 2011]

Dramatic improvement of DC-based immunotherapy against various malignancies

Yui Harada1,2, Yoshikazu Yonemitsu1

1R and D Laboratory for Innovative Biotherapeutics, Kyushu University Graduate School of Pharmaceutical Sciences, Fukuoka 812-8582, Japan, 2Departments of Urology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Dendritic cells
4. DCs in the immune system
5. DC vaccines for various malignancies - current status and problems
6. Solution for low efficacy 6.1. Stimuli
6.2. Dose of administered DCs 7. A new approach to the treatment of malignancies
8. Perspectives
9. Acknowledgments
10. References

1. ABSTRACT

Dendritic cells (DCs) play a crucial role in maintaining the immune system. Though DC-based cancer immunotherapy has been suggested as a potential treatment for various kinds of malignancies, clinical efficacies are still insufficient in many human trials. To identify the causes of the low efficacies, we paid attention to their numbers and how they are activated. We proved that DCs' antitumor effect depends on their number and the way they are activated. We here established a possible breakthrough, a simple cytokine-based culture method to realize a log-scale order of functional murine/human DCs. Moreover, we demonstrated that DCs activated by replication-deficient recombinant Sendai virus (rSeV) were dramatically more effective than that seen in the use of current DC vaccine for immunotherapy against malignancies. Our study could overcome these problems and would improve treatment of malignancies.