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Abstract A29: An Ad5 [E1-, E2b-] platform carrying the TAA CEA(6D) induces CEA directed CMI responses in patients with advanced CEA-expressing colorectal cancer in a phase I/II clinical trial..

Publication ,  Journal Article
Morse, MA; Gabitzsch, ES; Xu, Y; Rajesh, D; Nguyen, S; Balcaitis, S; Balint, JP; Jones, F
Published in: Cancer Research
January 1, 2013

First-generation, E1-deleted adenovirus (Ad)-based vectors, although promising platforms for use as cancer vaccines, are limited by the naturally occuring or induced Ad-specific neutralizing antibodies. We hypothesized that Ad5-based vectors with deletions of the E1 and the E2b regions (the latter encoding the DNA polymerase and the preterminal protein) would, by virtue of diminished late phase viral protein expression, avoid immunological clearance and induce more potent immune responses against the encoded tumor antigen transgene in Ad-immune hosts. In this translational study, we demonstrated that delivery of increasing doses of the Ad5 [E1-, E2b-]-CEA(6D) in mice resulted in CEA-specific cell-mediated immune (CMI) responses. In the follow-up human phase I/II study, escalating doses of the vaccine induced higher CEA-specific CMI responses despite the presence of pre-existing Ad5 immunity in a majority (76%) of patients. Importantly, there was minimal toxicity, and overall patient survival (54.1% at 12 months) was similar regardless of pre-existing Ad5 neutralizing antibody titers. The results demonstrate that the novel Ad5 [E1-, E2b-] gene delivery platform can both break tolerance and generate significant CMI responses to the TAA CEA in the setting of both naturally acquired Ad5-specific immunity and/or immunization-induced Ad5 immunity.Citation Format: Michael A. Morse, Elizabeth S. Gabitzsch, Younong Xu, Dua Rajesh, Susan Nguyen, Stephanie Balcaitis, Joseph P. Balint, Jr., Frank Jones. An Ad5 [E1-, E2b-] platform carrying the TAA CEA(6D) induces CEA directed CMI responses in patients with advanced CEA-expressing colorectal cancer in a phase I/II clinical trial.. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A29.

Duke Scholars

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

January 1, 2013

Volume

73

Issue

1_Supplement

Start / End Page

A29 / A29

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Morse, M. A., Gabitzsch, E. S., Xu, Y., Rajesh, D., Nguyen, S., Balcaitis, S., … Jones, F. (2013). Abstract A29: An Ad5 [E1-, E2b-] platform carrying the TAA CEA(6D) induces CEA directed CMI responses in patients with advanced CEA-expressing colorectal cancer in a phase I/II clinical trial.. Cancer Research, 73(1_Supplement), A29–A29. https://doi.org/10.1158/1538-7445.tumimm2012-a29
Morse, Michael A., Elizabeth S. Gabitzsch, Younong Xu, Dua Rajesh, Susan Nguyen, Stephanie Balcaitis, Joseph P. Balint, and Frank Jones. “Abstract A29: An Ad5 [E1-, E2b-] platform carrying the TAA CEA(6D) induces CEA directed CMI responses in patients with advanced CEA-expressing colorectal cancer in a phase I/II clinical trial..Cancer Research 73, no. 1_Supplement (January 1, 2013): A29–A29. https://doi.org/10.1158/1538-7445.tumimm2012-a29.
Morse, Michael A., et al. “Abstract A29: An Ad5 [E1-, E2b-] platform carrying the TAA CEA(6D) induces CEA directed CMI responses in patients with advanced CEA-expressing colorectal cancer in a phase I/II clinical trial..Cancer Research, vol. 73, no. 1_Supplement, American Association for Cancer Research (AACR), Jan. 2013, pp. A29–A29. Crossref, doi:10.1158/1538-7445.tumimm2012-a29.
Morse MA, Gabitzsch ES, Xu Y, Rajesh D, Nguyen S, Balcaitis S, Balint JP, Jones F. Abstract A29: An Ad5 [E1-, E2b-] platform carrying the TAA CEA(6D) induces CEA directed CMI responses in patients with advanced CEA-expressing colorectal cancer in a phase I/II clinical trial.. Cancer Research. American Association for Cancer Research (AACR); 2013 Jan 1;73(1_Supplement):A29–A29.

Published In

Cancer Research

DOI

EISSN

1538-7445

ISSN

0008-5472

Publication Date

January 1, 2013

Volume

73

Issue

1_Supplement

Start / End Page

A29 / A29

Publisher

American Association for Cancer Research (AACR)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis