Tumor Therapy Applying Membrane-bound Form of Cytokines

Abstract

Tumor therapy using cytokines has been developed for last two decades. Several recombinant cytokines and tumor cell vaccines produced by cytokine gene transfer have been in clinical trials, but several side effects hamper routine clinical applications. Many cytokines are originally expressed as membrane-bound form and then processed to secretory form exerting paracrine effects. Though functional differences of these two types of cytokines are elusive yet, the membrane-bound form of cytokine may exert its effects on restricted target cells as a juxtacrine, which are in physical contacts. With the efforts to improve antitumor activities of cytokines in cancer patients, developing new strategies to alleviate life-threatening side effects became an inevitable goal of tumor immunologists. Among these, tumor cell vaccines expressing cytokines as membrane-bound form on tumor cell surface have been developed by genetic engineering techniques with the hope of selective stimulation of the target cells that are in cell-to-cell contacts. In this review, recent progress of tumor cell vaccines expressing membrane-bound form of cytokines will be discussed.

Keywords: CTL; membrane-bound form of cytokine; tumor therapy.

Figure 1

The mbCytokines on tumor cell vaccines may provide costimulatory signal to fulfill the requirements for tumor specific CTL activation. The tumor cell vaccine expressing mbCytokine fulfills the two signals required for T cell activation as in (B), but most tumor cells lack proper costimulatory molecules as in (A). If costimulatory molecules, in this case mbCytokine, are provided, the CTL precursors in physical contact with tumor cells may acquire full signals by direct priming, and lead to tumor-specific CTL activation selectively.