History of Oncolytic Viruses: Genesis to Genetic Engineering

Abstract

Since the turn of the nineteenth century, when their existence was first recognized, viruses have attracted considerable interest as possible agents of tumor destruction. Early case reports emphasized regression of cancers during naturally acquired virus infections, providing the basis for clinical trials where body fluids containing human or animal viruses were used to transmit infections to cancer patients. Most often the viruses were arrested by the host immune system and failed to impact tumor growth, but sometimes, in immunosuppressed patients, infection persisted and tumors regressed, although morbidity as a result of the infection of normal tissues was unacceptable. With the advent of rodent models and new methods for virus propagation, there were numerous attempts through the 1950s and 1960s to force the evolution of viruses with greater tumor specificity, but success was limited and many researchers abandoned the field. Technology employing reverse genetics later brought about a renewal of interest in virotherapy that allowed the generation of more potent, tumor-specific oncolytics. Here, examination of early oncolytic virotherapy before genetic engineering serves to highlight tremendous advances, yet also hints at ways to penetrate host immune defenses, a significant remaining challenge in modern virotherapy research.

Assessment of an altered E1B promoter on the specificity and potency of triple-regulated conditionally replicating adenoviruses: implications for the generation of ideal m-CRAs

“…1,2 CRAs are predominantly classified into two categories. 3 The first CRA category has attenuated viral replication only in normal cells because of specific mutations in the adenoviral early gene 1 (E1), such as E1AD24 and E1BD55K that lack the Rb-and p53-binding sites in the early region 1A (E1A) and 1B (E1B), respectively.…”

Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth

“…21,22 There are several oncolytic viruses that have shown promise for the treatment of MM and they are discussed below.…”

Anticancer Gene Transfer for Cancer Gene Therapy

“…Throughout the recorded history of diseases, there have been observations of cancer regression upon natural co-infection with viruses (Sinkovics and Horvath, 1993;Kelly and Russell, 2007). During the early twentieth century, based on these observations, several clinical trials were conducted via fluid transfer from animal or human bodies that were infected with viruses to infect patients with cancer (Hoster et al, 1949).…”