High scFv-receptor affinity does not enhance the antitumor activity of HER2-retargeted measles virus

L. Suksanpaisan; S. J. Russell; K. W. Peng

doi:10.1038/cgt.2014.25

High scFv-receptor affinity does not enhance the antitumor activity of HER2-retargeted measles virus

L. Suksanpaisan, S. J. Russell, K. W. Peng

Molecular Medicine

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

The relationship between ligand-receptor affinity and antitumor potency of an oncolytic virus was investigated using a panel of six HER2/neu (HER2)-targeted measles viruses (MVs) displaying single-chain antibodies (scFv) that bind to the same epitope on HER2, but with affinities ranging from 10 ^-6 to 10^-11 M. All viruses were able to infect SKOV3ip.1 human ovarian cancer cells in vitro, but only the high-affinity MV (Kd ≥10^-8 M) induced cytopathic effects of syncytia formation in the cell monolayers. In contrast, all six viruses were therapeutically active in vivo against orthotopic human ovarian SKOV3ip.1 tumor xenografts in athymic mice compared with saline-treated controls. The oncolytic activities of MV displaying the high-affinity scFv (Kd=10^-9, 10^-10, 10 ^-11 M) were not significantly superior to MV displaying scFv with Kd of 10^-8 M or less. Results from this study suggest that increasing the receptor affinity of the attachment protein of an oncolytic MV has minimal impact on its in vivo efficacy against a tumor that expresses the targeted receptor.

Original language	English (US)
Pages (from-to)	256-260
Number of pages	5
Journal	Cancer Gene Therapy
Volume	21
Issue number	6
DOIs	https://doi.org/10.1038/cgt.2014.25
State	Published - Jun 2014

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Cancer Research

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10.1038/cgt.2014.25

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title = "High scFv-receptor affinity does not enhance the antitumor activity of HER2-retargeted measles virus",

abstract = "The relationship between ligand-receptor affinity and antitumor potency of an oncolytic virus was investigated using a panel of six HER2/neu (HER2)-targeted measles viruses (MVs) displaying single-chain antibodies (scFv) that bind to the same epitope on HER2, but with affinities ranging from 10 -6 to 10-11 M. All viruses were able to infect SKOV3ip.1 human ovarian cancer cells in vitro, but only the high-affinity MV (Kd ≥10-8 M) induced cytopathic effects of syncytia formation in the cell monolayers. In contrast, all six viruses were therapeutically active in vivo against orthotopic human ovarian SKOV3ip.1 tumor xenografts in athymic mice compared with saline-treated controls. The oncolytic activities of MV displaying the high-affinity scFv (Kd=10-9, 10-10, 10 -11 M) were not significantly superior to MV displaying scFv with Kd of 10-8 M or less. Results from this study suggest that increasing the receptor affinity of the attachment protein of an oncolytic MV has minimal impact on its in vivo efficacy against a tumor that expresses the targeted receptor.",

author = "L. Suksanpaisan and Russell, {S. J.} and Peng, {K. W.}",

note = "Funding Information: This work is supported by grants from the National Institutes of Health/National Cancer Institutes (R01CA118488, R01CA129193 and R01CA129966).",

year = "2014",

month = jun,

doi = "10.1038/cgt.2014.25",

language = "English (US)",

volume = "21",

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AU - Suksanpaisan, L.

AU - Russell, S. J.

AU - Peng, K. W.

N1 - Funding Information: This work is supported by grants from the National Institutes of Health/National Cancer Institutes (R01CA118488, R01CA129193 and R01CA129966).

PY - 2014/6

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N2 - The relationship between ligand-receptor affinity and antitumor potency of an oncolytic virus was investigated using a panel of six HER2/neu (HER2)-targeted measles viruses (MVs) displaying single-chain antibodies (scFv) that bind to the same epitope on HER2, but with affinities ranging from 10 -6 to 10-11 M. All viruses were able to infect SKOV3ip.1 human ovarian cancer cells in vitro, but only the high-affinity MV (Kd ≥10-8 M) induced cytopathic effects of syncytia formation in the cell monolayers. In contrast, all six viruses were therapeutically active in vivo against orthotopic human ovarian SKOV3ip.1 tumor xenografts in athymic mice compared with saline-treated controls. The oncolytic activities of MV displaying the high-affinity scFv (Kd=10-9, 10-10, 10 -11 M) were not significantly superior to MV displaying scFv with Kd of 10-8 M or less. Results from this study suggest that increasing the receptor affinity of the attachment protein of an oncolytic MV has minimal impact on its in vivo efficacy against a tumor that expresses the targeted receptor.

AB - The relationship between ligand-receptor affinity and antitumor potency of an oncolytic virus was investigated using a panel of six HER2/neu (HER2)-targeted measles viruses (MVs) displaying single-chain antibodies (scFv) that bind to the same epitope on HER2, but with affinities ranging from 10 -6 to 10-11 M. All viruses were able to infect SKOV3ip.1 human ovarian cancer cells in vitro, but only the high-affinity MV (Kd ≥10-8 M) induced cytopathic effects of syncytia formation in the cell monolayers. In contrast, all six viruses were therapeutically active in vivo against orthotopic human ovarian SKOV3ip.1 tumor xenografts in athymic mice compared with saline-treated controls. The oncolytic activities of MV displaying the high-affinity scFv (Kd=10-9, 10-10, 10 -11 M) were not significantly superior to MV displaying scFv with Kd of 10-8 M or less. Results from this study suggest that increasing the receptor affinity of the attachment protein of an oncolytic MV has minimal impact on its in vivo efficacy against a tumor that expresses the targeted receptor.

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High scFv-receptor affinity does not enhance the antitumor activity of HER2-retargeted measles virus

Abstract

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