A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer

Yuman Fong, Teresa Kim, Amit Bhargava, Larry Schwartz, Karen Brown, Lynn Brody, Anne Covey, Matthias Karrasch, George Getrajdman, Axel Mescheder, William Jarnagin, Nancy Kemeny

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Genetically engineered herpes simplex viruses (HSVs) can selectively infect and replicate in cancer cells, and are candidates for use as oncolytic therapy. This long-term report of a phase I trial examines vascular administration of HSV as therapy for cancer. Twelve subjects with metastatic colorectal cancer within the liver failing first-line chemotherapy were treated in four cohorts with a single dose (3 × 106 to 1 × 108 particles) of NV1020, a multimutated, replication-competent HSV. After hepatic arterial administration, subjects were observed for 4 weeks before starting intra-arterial chemotherapy. All patients exhibited progression of disease before HSV injection. During observation, levels of the tumor marker carcinoembryonic antigen (CEA) decreased (median % drop = 24%; range 13-74%; P < 0.02). One of three individuals at the 108 level showed a 39% radiologic decrease in tumor size by cross-section and 75% by volume. HSV infection was documented from liver tumor biopsies. After beginning regional chemotherapy, all patients demonstrated a further decrease in CEA (median 96%; range 50-98%; P < 0.008) and a radiologic partial response. Median survival for this group was 25 months. During follow-up, no signs of virus reactivation were found. Multimutated HSV can be delivered safely into the human bloodstream to produce selective infection of tumor tissues and biologic effects.

Original languageEnglish (US)
Pages (from-to)389-394
Number of pages6
JournalMolecular Therapy
Volume17
Issue number2
DOIs
StatePublished - 2009

Fingerprint

Oncolytic Viruses
Simplexvirus
Colorectal Neoplasms
Carcinoembryonic Antigen
Neoplasms
Drug Therapy
Liver
Differentiation Antigens
Neoplasm Antigens
Virus Diseases
Liver Neoplasms
Tumor Biomarkers
Blood Vessels
Disease Progression
Observation
Viruses
Biopsy
Injections
Survival
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology
  • Medicine(all)

Cite this

Fong, Y., Kim, T., Bhargava, A., Schwartz, L., Brown, K., Brody, L., ... Kemeny, N. (2009). A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer. Molecular Therapy, 17(2), 389-394. https://doi.org/10.1038/mt.2008.240

A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer. / Fong, Yuman; Kim, Teresa; Bhargava, Amit; Schwartz, Larry; Brown, Karen; Brody, Lynn; Covey, Anne; Karrasch, Matthias; Getrajdman, George; Mescheder, Axel; Jarnagin, William; Kemeny, Nancy.

In: Molecular Therapy, Vol. 17, No. 2, 2009, p. 389-394.

Research output: Contribution to journalArticle

Fong, Y, Kim, T, Bhargava, A, Schwartz, L, Brown, K, Brody, L, Covey, A, Karrasch, M, Getrajdman, G, Mescheder, A, Jarnagin, W & Kemeny, N 2009, 'A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer', Molecular Therapy, vol. 17, no. 2, pp. 389-394. https://doi.org/10.1038/mt.2008.240
Fong, Yuman ; Kim, Teresa ; Bhargava, Amit ; Schwartz, Larry ; Brown, Karen ; Brody, Lynn ; Covey, Anne ; Karrasch, Matthias ; Getrajdman, George ; Mescheder, Axel ; Jarnagin, William ; Kemeny, Nancy. / A herpes oncolytic virus can be delivered via the vasculature to produce biologic changes in human colorectal cancer. In: Molecular Therapy. 2009 ; Vol. 17, No. 2. pp. 389-394.
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