Adenoviruses with an RGD-4C modification of the fiber knob elicit a neutralizing antibody response but continue to allow enhanced gene delivery

Minghui Wang, Akseli Hemminki, Gene P. Siegal, Mack N. Barnes, Igor Dmitriev, Victor Krasnykh, Bin Liu, David T. Curiel, Ronald D. Alvarez

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The purpose of this study was to investigate the effect of preexisting neutralizing antibody (NAbs) in naive mice and the effect of induced NAbs in mice immunized with either an RGD or nonmodified Ad5 vector on the transduction efficiency of adenoviral vectors. BALB/c mice were immunized with Ad5LucRGD, with the unmodified Ad5Luc1, or with Opti-MEM intraperitoneally (ip) from one to three times. Sera were collected on day 27 and serially diluted to block Ad5Luc1 or Ad5LucRGD prior to infection of SKOV3.ip1 human ovarian carcinoma cells with these same vectors. Forty-eight hours post Ad infection, a luciferase assay was performed to determine the titer of NAbs. Luciferase assay data showed that the gene transfer efficacy of Ad5LucRGD was 1.56-fold higher than Ad5Luc1 in the presence of serum from naive mice. In the presence of serum from Ad5Luc1-challenged mice, the transduction efficiency of Ad5LucRGD was 3.27-fold higher (single challenge) and 4.2-fold higher (triple challenge) than Ad5Luc1. In the presence of serum from Ad5LucRGD-challenged mice, the transduction efficiency of Ad5LucRGD was 2.24-fold higher (single challenge) and 2.53-fold higher (triple challenge) than Ad5Luc1. The RGD-modified human Ad vectors appear to be less recognizable than unmodified Ad to preexisting NAbs in mouse models. RGD-modified Ad vectors also appear to elicit a relatively lower level of NAbs that may also contribute to the higher gene transduction efficiency of these modified vectors. Therefore, RGD-modified Ad vectors may be reagents of clinical utility in the context of preformed anti-Ad immunity and in the setting of repetitive dosing.

Original languageEnglish (US)
Pages (from-to)341-348
Number of pages8
JournalGynecologic oncology
Volume96
Issue number2
DOIs
StatePublished - Feb 1 2005

Fingerprint

Neutralizing Antibodies
Adenoviridae
Antibody Formation
Genes
Luciferases
Serum
Infection
Immunity
Carcinoma

Keywords

  • Adenoviruses
  • Neutralizing antibody
  • RGD-4C

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

Adenoviruses with an RGD-4C modification of the fiber knob elicit a neutralizing antibody response but continue to allow enhanced gene delivery. / Wang, Minghui; Hemminki, Akseli; Siegal, Gene P.; Barnes, Mack N.; Dmitriev, Igor; Krasnykh, Victor; Liu, Bin; Curiel, David T.; Alvarez, Ronald D.

In: Gynecologic oncology, Vol. 96, No. 2, 01.02.2005, p. 341-348.

Research output: Contribution to journalArticle

Wang, M, Hemminki, A, Siegal, GP, Barnes, MN, Dmitriev, I, Krasnykh, V, Liu, B, Curiel, DT & Alvarez, RD 2005, 'Adenoviruses with an RGD-4C modification of the fiber knob elicit a neutralizing antibody response but continue to allow enhanced gene delivery', Gynecologic oncology, vol. 96, no. 2, pp. 341-348. https://doi.org/10.1016/j.ygyno.2004.09.063
Wang, Minghui ; Hemminki, Akseli ; Siegal, Gene P. ; Barnes, Mack N. ; Dmitriev, Igor ; Krasnykh, Victor ; Liu, Bin ; Curiel, David T. ; Alvarez, Ronald D. / Adenoviruses with an RGD-4C modification of the fiber knob elicit a neutralizing antibody response but continue to allow enhanced gene delivery. In: Gynecologic oncology. 2005 ; Vol. 96, No. 2. pp. 341-348.
@article{67a73ed2655d4681815665ecf9bb34ff,
title = "Adenoviruses with an RGD-4C modification of the fiber knob elicit a neutralizing antibody response but continue to allow enhanced gene delivery",
abstract = "The purpose of this study was to investigate the effect of preexisting neutralizing antibody (NAbs) in naive mice and the effect of induced NAbs in mice immunized with either an RGD or nonmodified Ad5 vector on the transduction efficiency of adenoviral vectors. BALB/c mice were immunized with Ad5LucRGD, with the unmodified Ad5Luc1, or with Opti-MEM intraperitoneally (ip) from one to three times. Sera were collected on day 27 and serially diluted to block Ad5Luc1 or Ad5LucRGD prior to infection of SKOV3.ip1 human ovarian carcinoma cells with these same vectors. Forty-eight hours post Ad infection, a luciferase assay was performed to determine the titer of NAbs. Luciferase assay data showed that the gene transfer efficacy of Ad5LucRGD was 1.56-fold higher than Ad5Luc1 in the presence of serum from naive mice. In the presence of serum from Ad5Luc1-challenged mice, the transduction efficiency of Ad5LucRGD was 3.27-fold higher (single challenge) and 4.2-fold higher (triple challenge) than Ad5Luc1. In the presence of serum from Ad5LucRGD-challenged mice, the transduction efficiency of Ad5LucRGD was 2.24-fold higher (single challenge) and 2.53-fold higher (triple challenge) than Ad5Luc1. The RGD-modified human Ad vectors appear to be less recognizable than unmodified Ad to preexisting NAbs in mouse models. RGD-modified Ad vectors also appear to elicit a relatively lower level of NAbs that may also contribute to the higher gene transduction efficiency of these modified vectors. Therefore, RGD-modified Ad vectors may be reagents of clinical utility in the context of preformed anti-Ad immunity and in the setting of repetitive dosing.",
keywords = "Adenoviruses, Neutralizing antibody, RGD-4C",
author = "Minghui Wang and Akseli Hemminki and Siegal, {Gene P.} and Barnes, {Mack N.} and Igor Dmitriev and Victor Krasnykh and Bin Liu and Curiel, {David T.} and Alvarez, {Ronald D.}",
year = "2005",
month = "2",
day = "1",
doi = "10.1016/j.ygyno.2004.09.063",
language = "English (US)",
volume = "96",
pages = "341--348",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Adenoviruses with an RGD-4C modification of the fiber knob elicit a neutralizing antibody response but continue to allow enhanced gene delivery

AU - Wang, Minghui

AU - Hemminki, Akseli

AU - Siegal, Gene P.

AU - Barnes, Mack N.

AU - Dmitriev, Igor

AU - Krasnykh, Victor

AU - Liu, Bin

AU - Curiel, David T.

AU - Alvarez, Ronald D.

PY - 2005/2/1

Y1 - 2005/2/1

N2 - The purpose of this study was to investigate the effect of preexisting neutralizing antibody (NAbs) in naive mice and the effect of induced NAbs in mice immunized with either an RGD or nonmodified Ad5 vector on the transduction efficiency of adenoviral vectors. BALB/c mice were immunized with Ad5LucRGD, with the unmodified Ad5Luc1, or with Opti-MEM intraperitoneally (ip) from one to three times. Sera were collected on day 27 and serially diluted to block Ad5Luc1 or Ad5LucRGD prior to infection of SKOV3.ip1 human ovarian carcinoma cells with these same vectors. Forty-eight hours post Ad infection, a luciferase assay was performed to determine the titer of NAbs. Luciferase assay data showed that the gene transfer efficacy of Ad5LucRGD was 1.56-fold higher than Ad5Luc1 in the presence of serum from naive mice. In the presence of serum from Ad5Luc1-challenged mice, the transduction efficiency of Ad5LucRGD was 3.27-fold higher (single challenge) and 4.2-fold higher (triple challenge) than Ad5Luc1. In the presence of serum from Ad5LucRGD-challenged mice, the transduction efficiency of Ad5LucRGD was 2.24-fold higher (single challenge) and 2.53-fold higher (triple challenge) than Ad5Luc1. The RGD-modified human Ad vectors appear to be less recognizable than unmodified Ad to preexisting NAbs in mouse models. RGD-modified Ad vectors also appear to elicit a relatively lower level of NAbs that may also contribute to the higher gene transduction efficiency of these modified vectors. Therefore, RGD-modified Ad vectors may be reagents of clinical utility in the context of preformed anti-Ad immunity and in the setting of repetitive dosing.

AB - The purpose of this study was to investigate the effect of preexisting neutralizing antibody (NAbs) in naive mice and the effect of induced NAbs in mice immunized with either an RGD or nonmodified Ad5 vector on the transduction efficiency of adenoviral vectors. BALB/c mice were immunized with Ad5LucRGD, with the unmodified Ad5Luc1, or with Opti-MEM intraperitoneally (ip) from one to three times. Sera were collected on day 27 and serially diluted to block Ad5Luc1 or Ad5LucRGD prior to infection of SKOV3.ip1 human ovarian carcinoma cells with these same vectors. Forty-eight hours post Ad infection, a luciferase assay was performed to determine the titer of NAbs. Luciferase assay data showed that the gene transfer efficacy of Ad5LucRGD was 1.56-fold higher than Ad5Luc1 in the presence of serum from naive mice. In the presence of serum from Ad5Luc1-challenged mice, the transduction efficiency of Ad5LucRGD was 3.27-fold higher (single challenge) and 4.2-fold higher (triple challenge) than Ad5Luc1. In the presence of serum from Ad5LucRGD-challenged mice, the transduction efficiency of Ad5LucRGD was 2.24-fold higher (single challenge) and 2.53-fold higher (triple challenge) than Ad5Luc1. The RGD-modified human Ad vectors appear to be less recognizable than unmodified Ad to preexisting NAbs in mouse models. RGD-modified Ad vectors also appear to elicit a relatively lower level of NAbs that may also contribute to the higher gene transduction efficiency of these modified vectors. Therefore, RGD-modified Ad vectors may be reagents of clinical utility in the context of preformed anti-Ad immunity and in the setting of repetitive dosing.

KW - Adenoviruses

KW - Neutralizing antibody

KW - RGD-4C

UR - http://www.scopus.com/inward/record.url?scp=12344257588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12344257588&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2004.09.063

DO - 10.1016/j.ygyno.2004.09.063

M3 - Article

C2 - 15661219

AN - SCOPUS:12344257588

VL - 96

SP - 341

EP - 348

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 2

ER -