Clinical studies of viruses as antineoplastic agents, with particular reference to egypt 101 virus

Southam, Chester M.; Moore, Alice E.

doi:10.1002/1097-0142(195209)5:5<1025::aid-cncr2820050518>3.0.co;2-q

Cited by 162 publications

(60 citation statements)

References 13 publications

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“…27 In this case, the results were a little more encouraging, as three of five treated patients who acquired symptoms of glandular trials against a wide range of cancers (Table 1). 36,38 Viremia and intra-tumoral virus replication were confirmed in most patients, but tumor responses were rare. Immunosuppressed patients with leukemia or lymphoma were more likely to respond to therapy, but were also at higher risk of fatal neurotoxicity.…”

Section: Human Pathogensmentioning

confidence: 99%

“…Also at this time, Alice Moore, who pioneered the testing of oncolytic viruses in animal cancer models (see below), teamed up with Chester Southam, now considered a rather overzealous clinical oncologist, 35 at Memorial Sloan-Kettering hospital. As the dominant players of that era in the field, Southam and Moore [36][37][38][39][40][41][42][43][44] contributed much in the form of both preclinical trials with animal models and clinical trials employing oncolytic viruses, but perhaps even more so in terms of cautionary tales of transitioning from bench to bedside.…”

Section: Human Pathogensmentioning

confidence: 99%

“…[36][37][38][40][41][42]45,46 The Egypt 101 isolate of West Nile virus was used in more than 150 virus therapy Chester Southam expected, responses were diminished in patients with pre-existing anti-adenovirus antibodies, emphasizing the problem of premature immune-mediated virus elimination. Though investigation into adenovirus for the treatment of cervical cancer continued, 49,50 in the absence of any useful prolongation of survival, it slowed to a trickle.…”

Section: Human Pathogensmentioning

confidence: 99%

“…In the years that followed, many other human pathogens were investigated for oncolytic activity employing rodent models, including Bunyamwera, Ilheus, dengue, yellow fever, West Nile virus 41,42 and its Egypt 101 isolate, 36 Semliki Forest virus, mumps, vaccinia, 62 and adenovirus. 48,63 As previously discussed, many of these were also evaluated in clinical trials that served primarily to demonstrate that complete tumor regression was much more likely to occur in the mouse than in the patient, 41,48,62,63 bringing into question the relevance of the responses seen in heterotransplanted cancer tissues in the mouse model.…”

Section: In Vivo Cancer Models: Virotherapy Becomes a Sciencementioning

confidence: 99%

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History of Oncolytic Viruses: Genesis to Genetic Engineering

2007

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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.

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Section: Human Pathogensmentioning

confidence: 99%

Section: Human Pathogensmentioning

confidence: 99%

Section: Human Pathogensmentioning

confidence: 99%

Section: In Vivo Cancer Models: Virotherapy Becomes a Sciencementioning

confidence: 99%

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History of Oncolytic Viruses: Genesis to Genetic Engineering

2007

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“…He documented the cause of tumor regression induced by these viruses. [12][13][14][15][16] Mechanisms of the oncolytic effect The oncolytic effect has several possible mechanisms that yield complex results. The first such mechanism is the result of viral replication within the cell and rupture out of the cell.…”

Section: Historical Backgroundmentioning

confidence: 99%

The potential of oncolytic virus therapy for pancreatic cancer

et al. 2005

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The objective of this paper was to review a new category of gene therapy using oncolytic viruses for the treatment of pancreatic cancer. The eligibility and feasibility of oncolytic virus therapy as a novel therapeutic agent against pancreatic cancer are discussed as well as basic research for clinical trials, including a historical perspective and the current status of these novel agents. Even combination therapy, such as surgery with radiation and chemotherapy, has not significantly improved the survival rate of pancreatic cancer. Recently, a clinical trial (phase I and II) using an oncolytic adenovirus, ONYX-015, was completed in patients with pancreatic cancer. The phase II trial yielded beneficial results (tumor reduction or stabilization) in about 50% of the patients. A phase I study of the efficacy of oncolytic herpes viruses, G207, OncoVEX GM-CSF, and 1716 against a variety of tumors has been completed, and G207 is in phase II trials for use against brain tumors. In addition, a phase I trial using the herpesvirus showed good tolerance at all dosages. We discuss the basic scientific principles and current results of the above clinical trials with respect to these oncolytic viruses, and then compare the relative advantages and disadvantages of adenoviruses and herpesviruses as oncolytic agents. We also review the published literature on newly developed oncolytic viruses. The concept of oncolytic therapy has been studied for a century. Recent technological developments have made these oncolytic viruses more tumor-specific by exploiting the tumor cell environments. In addition, these viruses have been reported to increase the immunosusceptibility of the tumor cells, and have been designed to express other genes to increase the susceptibility of tumor cells to other therapeutic agents. Oncolytic virus therapy certainly appears to be a feasible treatment for pancreatic cancer.

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Infectious Diseases

Reimann¹

1954

AMA Arch Intern Med

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Clinical studies of viruses as antineoplastic agents, with particular reference to egypt 101 virus

Cited by 162 publications

References 13 publications

History of Oncolytic Viruses: Genesis to Genetic Engineering

History of Oncolytic Viruses: Genesis to Genetic Engineering

The potential of oncolytic virus therapy for pancreatic cancer

Infectious Diseases

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