Gene and virotherapy for hematological malignancies.
Recent years have seen a transformation in the treatment of hematological malignancies. Advances in gene therapy and molecular techniques and significant gains in computational abilities have supported the rapid development of safer and better tolerated therapies for many patients with hematologic cancers. In this review, we discuss novel applications of gene therapy, including immunomodulation and gene silencing, and report on the rise of oncolytic viruses for use in the treatment of malignancies arising in cells of the blood, lymph, and marrow. We discuss the relationship of the tropism of wildtype viruses and their oncolytic behavior as well as the tumoricidal and immunostimulatory properties of a number of attenuated and recombinant viruses currently in clinical development in countries around the world. While we have focused on promising virotherapy applications for future development, we also present a historical perspective and identify areas of potential clinical and regulatory practice change. We outline several of the virus systems being developed for applications in hematology, and summarize efficacy data in the context of ongoing or future human clinical testing. We also present the advantages and limitations of gene and virus therapy, including challenges and opportunities for improved treatment tolerability and outcomes for patients with hematologic malignancies.
Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
Evidio
E
Domingo-Musibay
Division of Basic and Translational Research, Department of Surgery, University of Minnesota, MoosT 11-210, MMC195, 515 Delaware St SE, Minneapolis, MN, 55455, USA. yamam016@umn.edu.|Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. yamam016@umn.edu.
Masato
M
Yamamoto
D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D019337:Hematologic Neoplasms / Q000235:genetics / Q000628:therapy*; D006801:Humans; D050130:Oncolytic Virotherapy / Q000379:methods* / Q000639:trends; D016896:Treatment Outcome
Clinical trials; Gene therapy; Immunovirotherapy; Purging; Virotherapy