Abstract
Cancer is still a formidable disease with high rates of morbidity and mortality, although a number of anti-cancer drug have been developed. Much attention has been paid on drug delivery system (DDS) and nanoparticles have been developed based on liposomes and polymeric micelles for target delivery of anti-cancer drugs to tumor tissue. However, chemotherapeutic reagents and molecular-targeting drugs have limitations. One of the limitations is that cancer cells which receive those molecules are killed but others are still alive. Another limitation is that cancer cells resistant to those drugs are frequently emerging. Disease recurrence is the most difficult problem in cancer treatment. To suppress the growth of residual or inoperable tumors, cancer immunotherapy has been developed, but it was not successful. By analyzing the mechanism of immunological tolerance in cancer, it is revealed that cancer can escape from host immune surveillance by suppressing effector immune cells using a variety of approaches. Recently, cancer immunotherapy is revived by the development of immune-checkpoint inhibitory therapy. In DDS field, activation of anti-tumor immunity is also considered to be absolutely necessary for cancer treatment. It is reported recently that systemic administration of liposomes incorporating tumor-antigen RNA is effective for cancer treatment because the liposomes can target antigen-presenting cells but not cancer cells. We discovered that inactivated Sendai virus (Hemagglutinating virus of Japan) particle (HVJ envelope; HVJ-E) has multiple anti-cancer activities including activation of anti-tumor immunity and cancer selective killing. The anti-tumor activities of HVJ-E mainly depends on retinoic acid-inducible gene-I (RIG-I) signaling pathway, which is a novel approach in the field of cancer therapy. Clinical trials to treat cancers using HVJ-E itself are ongoing. HVJ-E can convert DDS by incorporating therapeutic molecules inside the particle. Therapeutic molecules are directly introduced inside the various cells both in vitro and in vivo via membrane fusion. We are investigating the possibility of HVJ-E vector incorporating therapeutic molecules for next generation cancer therapy.
