Infection Control & Hospital Epidemiology (2019), 40,350–354 doi:10.1017/ice.2018.358
Review
Viral oncolytic immunotherapy in the war on cancer: Infection control considerations
Elizabeth V. Robilotti MD, MPH1,2,3, Asmita Kumar PhD4, Michael S. Glickman MD2,5,3 and Mini Kamboj MD1,2,3 1Division of Infection Control, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 2Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, 3Department of Medicine, Weill Cornell Medical College, New York, 4Research and Technology Management, Memorial Sloan Kettering Cancer Center New York, New York and 5Immunology Program, Sloan Kettering Institute, New York, New York
Abstract
Oncolytic viral immunotherapy is an emerging treatment modality for cancer that exploits in vivo replication and other viral properties to enhance immune killing of malignant cells. The potential for horizontal transmission of native or engineered oncolytic viruses creates several unique infection control challenges. In 2015, talimogene laherparepvec (TVEC) became the first agent in this class to gain FDA approval for treatment of melanoma, and several others are being developed. Although some data on the transmissibility of TVEC are available from clinical studies, the aftermarket or real-world experience remains limited. We conducted a PUBMED-based search of the medical literature focusing on the safety and risk of TVEC transmission to close contacts including healthcare workers. The findings are summarized in this review and are intended to provide infection preventionists with practical guidance on handling issues related to administration and care of patients receiving TVEC. Additionally, we describe the current mechanism for evaluating the risk related to similar new agents entering clini- cal trials at our institution. Development of standarized approaches for the safe administration and precautions for ongoing care, especially in immunocompromised patients, are essential to support the broad adoption of this novel therapy.
(Received 25 September 2018; accepted 11 December 2018) Use of live viruses in the treatment of cancer
The use of oncolytic viral immunotherapy is an emerging modality for cancer treatment. Certain viruses have innate tropism for cancer cells or can be genetically engineered to infect and, sub- sequently, enhance the recognition of tumor cells by the host immune system. This immune mediated tumor destruction is achieved via the induction of virus-specific antigens on tumor cells or via the increased expression of existing antigens.1 A second and direct mechanism for a viral anticancer effect involves virus- induced cytolytic killing of tumor cells, called oncolysis. Use of oncolytic viruses in combination with other immunotherapies, such as immune checkpoint inhibitors (ICIs), has catapulted this form of treatment to the forefront of novel cancer therapeutics.2,3 Although these advances hold immense promise, extension of infectious agents from the laboratory to the bedside invokes numerous infection prevention and control issues related to the risk of horizontal transmission of oncolytic viruses to other patients as well as the safety of healthcare workers (HCWs). These challenges mirror issues already familiar to infection preven- tionists, such as the use of live virus vaccines (eg, measles, mumps, and rubella
— MMR) in cancer patients and other immunosup-
pressed populations or their household contacts. Although the concept of viral immunotherapy dates back to the 1950s, talimogene laherparepvec (TVEC), commercially known as
Author for correspondence: Elizabeth V. Robilotti, Email:
robilote@mskcc.org Cite this article: Robilotti EV, et al. (2019). Viral oncolytic immunotherapy in the war
on cancer: Infection control considerations. Infection Control&Hospital Epidemiology, 40: 350–354,
https://doi.org/10.1017/ice.2018.358
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved.
IMLGYIC (AmGen, Newbury Park, CA), recently became the first oncolytic viral agent approved by the FDA in the United States for the treatment of unresectable melanoma.4 Since then, a variety of viral vectors have entered clinical investigation for a broad range of indications.2,5,6 The re-emergence of oncolytic viruses offers a unique opportunity for infection preventionists to contribute to safe delivery of effective therapies and to further the overarching clinical and research mission of improving cancer-related survival. As these agents become ubiquitous in clinical environments, guidelines to ensure safe administration are essential. In this review,wedescribe the existing data related to transmission
of the first FDA-approved oncolytic viral agent, TVEC, and we draw attention to practical issues involved in its administration to patients and their ongoing care. Additionally, we describe our systematic approach to evaluating oncolytic viral clinical trials from an infection prevention perspective atMemorial Sloan Kettering Cancer Center.
Talimogene laherparepvec (TVEC) —
Awatershed moment for oncolytic viral vector therapy occurred in 2015 with the FDA approval of TVEC, a genetically engineered herpes simplex virus (HSV-1). Derived from a wild-type strain of HSV-1 (JS
1), TVEC was originally isolated from cold sore
lesions and is indicated for the treatment of unresectable metastatic melanoma in Europe and the United States through direct injec- tion of visible and/or palpable tumors.7,8 Gene deletions engi- neered in TVEC block antigen presentation and eliminate neurovirulence to attenuate any off-target effects. TVEC is also modified to selectively proliferate within cancer cells and to reduce infectivity in noncancer cells.9,10 An important feature of the
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