| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892
At least two signals are required for the activation of naive T cells by antigen-bearing target cells: an antigen-specific signal, delivered through the T-cell receptor, and a costimulatory signal delivered through the T-cell surface molecule CD28 by its natural ligand B7-1. The immunological benefit of coexpression of B7 with target antigen has been demonstrated with the use of several retroviral systems to transfect antigen-bearing cells. Although engineering recombinant constructs with genes for two or more antigens can mediate the dual expression of those antigens, disadvantages of this approach include the time for construction of each desirable combination and the inability to control differential expression levels of each gene product. An alternative approach would utilize separate constructs that could be admixed appropriately before administration. In this report we describe the functional consequences of the admixture of recombinant vaccinia murine B7-1 (rV-B7) to recombinant vaccinia expressing the human carcinoembryonic antigen gene (rV-CEA). Coinfection of cells resulted in high levels of cell surface expression of both the CEA and B7 molecules. Immunization of mice with various ratios (1:3, 1:1, 3:1) of rV-CEA and rV-B7 demonstrated that an admixture of rV-CEA and rV-B7 at a 3:1 ratio resulted in the generation of optimal CEA-specific T-cell responses. Next, we examined the efficacy of this admixture on antitumor activity. Typically, injection of murine carcinoma cells expressing CEA leads to the death of the host. One immunization of C57BL/6 mice with rV-CEA:rV-B7 (3:1) resulted in no tumor establishment. In contrast, administration of rV-CEA or rV-B7 alone had little or no antitumor effects. These studies demonstrate the advantages of the use of recombinant vaccinia viruses to deliver B7 molecules in combination with a tumor-associated antigen. The availability of the rV-B7 single construct and the ability to alter the B7 ratio could also have potential utility when coinfecting rV-B7 with recombinant vaccinia viruses containing genes for infectious agents or other tumor-associated antigen genes.
1 To whom requests for reprints should be addressed, at Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Building 10, Room 8B07, 9000 Rockville Pike, Bethesda, MD 20892.
Received 5/ 2/95. Accepted 6/12/95.
This article has been cited by other articles:
|
|
 |
|
  H. L. Kaufman and C. R. Divgi Optimizing Prostate Cancer Treatment by Combining Local Radiation Therapy with Systemic Vaccination Clin. Cancer Res., October 1, 2005; 11(19): 6757 - 6762. [Full Text] [PDF]
|
|
|
|
|
|
J. L. Gulley, P. M. Arlen, A. Bastian, S. Morin, J. Marte, P. Beetham, K.-Y. Tsang, J. Yokokawa, J. W. Hodge, C. Menard, et al. Combining a Recombinant Cancer Vaccine with Standard Definitive Radiotherapy in Patients with Localized Prostate Cancer Clin. Cancer Res., May 1, 2005; 11(9): 3353 - 3362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Marshall, J. L. Gulley, P. M. Arlen, P. K. Beetham, K.-Y. Tsang, R. Slack, J. W. Hodge, S. Doren, D. W. Grosenbach, J. Hwang, et al. Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-TRICOM Alone and Sequentially With Vaccinia-CEA(6D)-TRICOM, With and Without Granulocyte-Macrophage Colony-Stimulating Factor, in Patients With Carcinoembryonic Antigen-Expressing Carcinomas J. Clin. Oncol., February 1, 2005; 23(4): 720 - 731. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Hodge, D. J. Poole, W. M. Aarts, A. Gomez Yafal, L. Gritz, and J. Schlom Modified Vaccinia Virus Ankara Recombinants Are as Potent as Vaccinia Recombinants in Diversified Prime and Boost Vaccine Regimens to Elicit Therapeutic Antitumor Responses Cancer Res., November 15, 2003; 63(22): 7942 - 7949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Hodge, D. W. Grosenbach, W. M. Aarts, D. J. Poole, and J. Schlom Vaccine Therapy of Established Tumors in the Absence of Autoimmunity Clin. Cancer Res., May 1, 2003; 9(5): 1837 - 1849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lazetic, S. R. Leong, J. C-C. Chang, R. Ong, G. Dawes, and J. Punnonen Chimeric Co-stimulatory Molecules That Selectively Act through CD28 or CTLA-4 on Human T Cells J. Biol. Chem., October 4, 2002; 277(41): 38660 - 38668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Grosenbach, J. C. Barrientos, J. Schlom, and J. W. Hodge Synergy of Vaccine Strategies to Amplify Antigen-specific Immune Responses and Antitumor Effects Cancer Res., June 1, 2001; 61(11): 4497 - 4505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. von Mehren, P. Arlen, J. Gulley, A. Rogatko, H. S. Cooper, N. J. Meropol, R. K. Alpaugh, M. Davey, S. McLaughlin, M. T. Beard, et al. The Influence of Granulocyte Macrophage Colony-Stimulating Factor and Prior Chemotherapy on the Immunological Response to a Vaccine (ALVAC-CEA B7.1) in Patients with Metastatic Carcinoma Clin. Cancer Res., May 1, 2001; 7(5): 1181 - 1191. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. W. Hodge, A. N. Rad, D. W. Grosenbach, H. Sabzevari, A. G. Yafal, L. Gritz, and J. Schlom Enhanced Activation of T Cells by Dendritic Cells Engineered to Hyperexpress a Triad of Costimulatory Molecules J Natl Cancer Inst, August 2, 2000; 92(15): 1228 - 1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. von Mehren, P. Arlen, K. Y. Tsang, A. Rogatko, N. Meropol, H. S. Cooper, M. Davey, S. McLaughlin, J. Schlom, and L. M. Weiner Pilot Study of a Dual Gene Recombinant Avipox Vaccine Containing Both Carcinoembryonic Antigen (CEA) and B7.1 Transgenes in Patients with Recurrent CEA-expressing Adenocarcinomas Clin. Cancer Res., June 1, 2000; 6(6): 2219 - 2228. [Abstract] [Full Text]
|
|
|
|
|
|
J. W. Hodge, H. Sabzevari, A. Gomez Yafal, L. Gritz, M. G. O. Lorenz, and J. Schlom A Triad of Costimulatory Molecules Synergize to Amplify T-Cell Activation Cancer Res., November 1, 1999; 59(22): 5800 - 5807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 P. M. Challita-Eid, M. L. Penichet, S.-U. Shin, T. Poles, N. Mosammaparast, K. Mahmood, D. J. Slamon, S. L. Morrison, and J. D. Rosenblatt A B7.1-Antibody Fusion Protein Retains Antibody Specificity and Ability to Activate Via the T Cell Costimulatory Pathway J. Immunol., April 1, 1998; 160(7): 3419 - 3426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Osanto Vaccine Trials for the Clinician: Prospects for Tumor Antigens Oncologist, October 1, 1997; 2(5): 284 - 299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Goedegebuure and T. J. Eberlein Vaccine Trials for the Clinician: Prospects for Viral and Non-Viral Vectors Oncologist, October 1, 1997; 2(5): 300 - 310. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
