Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies

Michal Bereta, Andrew Hayhurst, Mariusz Gajda, Paulina Chorobik, Marta Targosz, Janusz Marcinkiewicz, Howard L. Kaufman

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Genetically modified Salmonella typhimurium VNP20009 (VNP) is a useful vehicle for cancer therapy and vaccine development but exhibits limited tumor targeting in vivo. We engineered a novel VNP derivative that expressed carcinoembryonic antigen (CEA)-specific single chain antibody fragments (scFv) on the cell surface to increase tumor-specific targeting. There was significant scFv cell surface display visualized by flow cytometry and confocal microscopy when cells were probed with fluorescently labeled CEA. Atomic force microscopy (AFM) measurements on whole bacteria confirmed binding of unlabeled CEA to the displayed scFv. The modified VNP strain exhibited increased localization in the upper gastrointestinal tract of CEA transgenic mice and accumulated in CEA-expressing tumors. Furthermore, treatment with a single dose of the VNP derivative inhibited growth of MC38CEA tumors and was associated with local accumulation of CD3+ T cells and CD11b+ macrophages. The display of antibody fragments on the surface of VNP represents a novel strategy for both targeting CEA-expressing tumors and increasing the immunogenicity of Salmonella-based vaccines for cancer.

Original languageEnglish (US)
Pages (from-to)4183-4192
Number of pages10
JournalVaccine
Volume25
Issue number21
DOIs
StatePublished - May 22 2007
Externally publishedYes

Fingerprint

Carcinoembryonic Antigen
surface antigens
Surface Antigens
Salmonella
therapeutics
neoplasms
antibodies
antigens
Antibodies
Neoplasms
Immunoglobulin Fragments
Therapeutics
Salmonella Vaccines
Single-Chain Antibodies
Cancer Vaccines
Upper Gastrointestinal Tract
Atomic Force Microscopy
Salmonella typhimurium
atomic force microscopy
Confocal Microscopy

Keywords

  • Cancer therapy
  • Carcinoembryonic antigen
  • Salmonella
  • scFv display
  • Vaccine vector

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Bereta, M., Hayhurst, A., Gajda, M., Chorobik, P., Targosz, M., Marcinkiewicz, J., & Kaufman, H. L. (2007). Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies. Vaccine, 25(21), 4183-4192. https://doi.org/10.1016/j.vaccine.2007.03.008

Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies. / Bereta, Michal; Hayhurst, Andrew; Gajda, Mariusz; Chorobik, Paulina; Targosz, Marta; Marcinkiewicz, Janusz; Kaufman, Howard L.

In: Vaccine, Vol. 25, No. 21, 22.05.2007, p. 4183-4192.

Research output: Contribution to journalArticle

Bereta, M, Hayhurst, A, Gajda, M, Chorobik, P, Targosz, M, Marcinkiewicz, J & Kaufman, HL 2007, 'Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies', Vaccine, vol. 25, no. 21, pp. 4183-4192. https://doi.org/10.1016/j.vaccine.2007.03.008
Bereta, Michal ; Hayhurst, Andrew ; Gajda, Mariusz ; Chorobik, Paulina ; Targosz, Marta ; Marcinkiewicz, Janusz ; Kaufman, Howard L. / Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies. In: Vaccine. 2007 ; Vol. 25, No. 21. pp. 4183-4192.
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