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Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients.

Publication ,  Journal Article
Morse, MA; Chaudhry, A; Gabitzsch, ES; Hobeika, AC; Osada, T; Clay, TM; Amalfitano, A; Burnett, BK; Devi, GR; Hsu, DS; Xu, Y; Balcaitis, S ...
Published in: Cancer Immunol Immunother
August 2013

First-generation, E1-deleted adenovirus subtype 5 (Ad5)-based vectors, although promising platforms for use as cancer vaccines, are impeded in activity by naturally occurring or induced Ad-specific neutralizing antibodies. Ad5-based vectors with deletions of the E1 and the E2b regions (Ad5 [E1-, E2b-]), the latter encoding the DNA polymerase and the pre-terminal protein, by virtue of diminished late phase viral protein expression, were hypothesized to avoid immunological clearance and induce more potent immune responses against the encoded tumor antigen transgene in Ad-immune hosts. Indeed, multiple homologous immunizations with Ad5 [E1-, E2b-]-CEA(6D), encoding the tumor antigen carcinoembryonic antigen (CEA), induced CEA-specific cell-mediated immune (CMI) responses with antitumor activity in mice despite the presence of preexisting or induced Ad5-neutralizing antibody. In the present phase I/II study, cohorts of patients with advanced colorectal cancer were immunized with escalating doses of Ad5 [E1-, E2b-]-CEA(6D). CEA-specific CMI responses were observed despite the presence of preexisting Ad5 immunity in a majority (61.3 %) of patients. Importantly, there was minimal toxicity, and overall patient survival (48 % at 12 months) was similar regardless of preexisting Ad5 neutralizing antibody titers. The results demonstrate that, in cancer patients, the novel Ad5 [E1-, E2b-] gene delivery platform generates significant CMI responses to the tumor antigen CEA in the setting of both naturally acquired and immunization-induced Ad5-specific immunity.

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Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

August 2013

Volume

62

Issue

8

Start / End Page

1293 / 1301

Location

Germany

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • T-Lymphocytes
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Interferon-gamma
  • Immunology
  • Immunization
  • Humans
 

Citation

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Chicago
ICMJE
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Morse, M. A., Chaudhry, A., Gabitzsch, E. S., Hobeika, A. C., Osada, T., Clay, T. M., … Lyerly, H. K. (2013). Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients. Cancer Immunol Immunother, 62(8), 1293–1301. https://doi.org/10.1007/s00262-013-1400-3
Morse, Michael A., Arvind Chaudhry, Elizabeth S. Gabitzsch, Amy C. Hobeika, Takuya Osada, Timothy M. Clay, Andrea Amalfitano, et al. “Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients.Cancer Immunol Immunother 62, no. 8 (August 2013): 1293–1301. https://doi.org/10.1007/s00262-013-1400-3.
Morse MA, Chaudhry A, Gabitzsch ES, Hobeika AC, Osada T, Clay TM, et al. Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients. Cancer Immunol Immunother. 2013 Aug;62(8):1293–301.
Morse, Michael A., et al. “Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients.Cancer Immunol Immunother, vol. 62, no. 8, Aug. 2013, pp. 1293–301. Pubmed, doi:10.1007/s00262-013-1400-3.
Morse MA, Chaudhry A, Gabitzsch ES, Hobeika AC, Osada T, Clay TM, Amalfitano A, Burnett BK, Devi GR, Hsu DS, Xu Y, Balcaitis S, Dua R, Nguyen S, Balint JP, Jones FR, Lyerly HK. Novel adenoviral vector induces T-cell responses despite anti-adenoviral neutralizing antibodies in colorectal cancer patients. Cancer Immunol Immunother. 2013 Aug;62(8):1293–1301.
Journal cover image

Published In

Cancer Immunol Immunother

DOI

EISSN

1432-0851

Publication Date

August 2013

Volume

62

Issue

8

Start / End Page

1293 / 1301

Location

Germany

Related Subject Headings

  • Treatment Outcome
  • Time Factors
  • T-Lymphocytes
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Interferon-gamma
  • Immunology
  • Immunization
  • Humans