This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kantor, J. Articles by Schlom, J. Search for Related Content PubMed PubMed Citation Articles by Kantor, J. Articles by Schlom, J.

Immunogenicity and Safety of a Recombinant Vaccinia Virus Vaccine Expressing the Carcinoembryonic Antigen Gene in a Nonhuman Primate

Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 [J. K., K. I., S. A., J. G., D. E., J. S.], and Bureau of Biologies, Food and Drug Administration, Bethesda, Maryland 20892 [P. S., R. O.]

² To whom requests for reprints should be addressed, at Laboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Building 10, Room 8B07, 9000 Rockville Pike, Bethesda, MD 20892.

We have previously reported the development of a recombinant vaccinia virus vaccine expressing the human carcinoembryonic antigen (CEA) gene, designated rV(NYC)-CEA. This construct has been shown to elicit specific anti-CEA immune responses and an antitumor effect in a murine tumor model. In the studies reported here, the safety and immunogenicity of this recombinant vaccinia virus were evaluated in a rhesus monkey model.

Human CEA is a M_r 180,000 glycoprotein expressed in approximately 90% of gastrointestinal carcinomas and in some breast and non-small cell lung carcinomas. This family also includes normal cross-reacting antigen (NCA). Rhesus monkeys, like humans, have some NCA on the surface of their granulocytes. Eight monkeys were immunized 3 or 4 times by skin scarification with the recombinant CEA vaccine and four monkeys received wild-type vaccinia virus as control.

After three vaccinations, all rV(NYC)-CEA-vaccinated animals exhibited a strong anti-CEA antibody response as measured by enzyme-linked immunosorbent assay. The functional ability of these antibodies to mediate lysis of a CEA-bearing tumor cell was demonstrated using human effector cells. This response could be enhanced by interleukin 2. Cellular immunity to CEA was measured by delayed-type hypersensitivity upon intradermal challenge with purified CEA. Only those animals receiving the recombinant vaccine displayed significant anti-CEA responses. Furthermore, peripheral blood mononuclear cells from immunized monkeys were found to proliferate in response to CEA stimulation. All vaccinated monkeys developed local skin irritation at the site of the vaccination, regional lymphadenopathy, and low-grade fevers after immunization. Following immunization with rV(NYC)-CEA, the response was consistent with the usual constitutional symptoms seen with human smallpox virus immunization. Blood counts, differentials, and hepatic and renal chemistries remained normal in all animals throughout the study and for up to 1 year following the primary vaccination. No evidence of immunological cross-reactivity to NCA was found by either a fall in the granulocyte count or analyses for anti-NCA antibodies. Thus, the rV(NYC)-CEA vaccine appears to be safe in rhesus monkeys. The administration of a CEA recombinant vaccine to rhesus monkeys induces both a humoral and a cell-mediated immune response directed against human CEA.

¹ Current address: Boston University Medical Center, Boston, MA 02118.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/13/92. Accepted 10/ 6/92.

This article has been cited by other articles:

				S. Kim-Schulze, H. S. Kim, A. Wainstein, D. W. Kim, W. C. Yang, D. Moroziewicz, P. Y. Mong, M. Bereta, B. Taback, Q. Wang, et al. Intrarectal Vaccination with Recombinant Vaccinia Virus Expressing Carcinoembronic Antigen Induces Mucosal and Systemic Immunity and Prevents Progression of Colorectal Cancer J. Immunol., December 1, 2008; 181(11): 8112 - 8119. [Abstract] [Full Text] [PDF]

				P. Correale, M. G. Cusi, K. Y. Tsang, M. T. Del Vecchio, S. Marsili, M. L. Placa, C. Intrivici, A. Aquino, L. Micheli, C. Nencini, et al. Chemo-Immunotherapy of Metastatic Colorectal Carcinoma With Gemcitabine Plus FOLFOX 4 Followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-2 Induces Strong Immunologic and Antitumor Activity in Metastatic Colon Cancer Patients J. Clin. Oncol., December 10, 2005; 23(35): 8950 - 8958. [Abstract] [Full Text] [PDF]

				J. A. McCart, J. M. Ward, J. Lee, Y. Hu, H. R. Alexander, S. K. Libutti, B. Moss, and D. L. Bartlett Systemic Cancer Therapy with a Tumor-selective Vaccinia Virus Mutant Lacking Thymidine Kinase and Vaccinia Growth Factor Genes Cancer Res., December 1, 2001; 61(24): 8751 - 8757. [Abstract] [Full Text] [PDF]

				J. L. Marshall, R. J. Hoyer, M. A. Toomey, K. Faraguna, P. Chang, E. Richmond, J. E. Pedicano, E. Gehan, R. A. Peck, P. Arlen, et al. Phase I Study in Advanced Cancer Patients of a Diversified Prime-and-Boost Vaccination Protocol Using Recombinant Vaccinia Virus and Recombinant Nonreplicating Avipox Virus to Elicit Anti-Carcinoembryonic Antigen Immune Responses J. Clin. Oncol., December 1, 2000; 18(23): 3964 - 3973. [Abstract] [Full Text] [PDF]

				R. M. Conry, K. O. Allen, S.-w. Lee, S. E. Moore, D. R. Shaw, and A. F. LoBuglio Human Autoantibodies to Carcinoembryonic Antigen (CEA) Induced by a Vaccinia-CEA Vaccine Clin. Cancer Res., January 1, 2000; 6(1): 34 - 41. [Abstract] [Full Text]

				R. M. Conry, M. B. Khazaeli, M. N. Saleh, K. O. Allen, D. L. Barlow, S. E. Moore, D. Craig, R. B. Arani, J. Schlom, and A. F. LoBuglio Phase I Trial of a Recombinant Vaccinia Virus Encoding Carcinoembryonic Antigen in Metastatic Adenocarcinoma: Comparison of Intradermal versus Subcutaneous Administration Clin. Cancer Res., September 1, 1999; 5(9): 2330 - 2337. [Abstract] [Full Text] [PDF]

				M. A. Morse, Y. Deng, D. Coleman, S. Hull, E. Kitrell-Fisher, S. Nair, J. Schlom, M.-E. Ryback, and H. K. Lyerly A Phase I Study of Active Immunotherapy with Carcinoembryonic Antigen Peptide (CAP-1)-pulsed, Autologous Human Cultured Dendritic Cells in Patients with Metastatic Malignancies Expressing Carcinoembryonic Antigen Clin. Cancer Res., June 1, 1999; 5(6): 1331 - 1338. [Abstract] [Full Text] [PDF]

				E. Kass, J. Schlom, J. Thompson, F. Guadagni, P. Graziano, and J. W. Greiner Induction of Protective Host Immunity to Carcinoembryonic Antigen (CEA), a Self-Antigen in CEA Transgenic Mice, by Immunizing with a Recombinant Vaccinia-CEA Virus Cancer Res., February 1, 1999; 59(3): 676 - 683. [Abstract] [Full Text] [PDF]

				K. A. Foon, J. Yannelli, and M. Bhattacharya-Chatterjee Colorectal Cancer as a Model for Immunotherapy Clin. Cancer Res., February 1, 1999; 5(2): 225 - 236. [Full Text] [PDF]

				J. L. Marshall, M. J. Hawkins, K. Y. Tsang, E. Richmond, J. E. Pedicano, M. Zhu, and J. Schlom Phase I Study in Cancer Patients of a Replication-Defective Avipox Recombinant Vaccine That Expresses Human Carcinoembryonic Antigen J. Clin. Oncol., January 1, 1999; 17(1): 332 - 332. [Abstract] [Full Text] [PDF]