Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine

Ky, Tsang; Zaremba, Sam; Ca, Nieroda; Mz, Zhu; Jm, Hamilton; Schlom, Jeffrey

doi:10.1093/jnci/87.13.982

Cited by 432 publications

(229 citation statements)

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“…33,34 Although replication-competent vaccinia virus vectors have been used in cancer immunotherapy trials in humans, [45][46][47][48] their use is undesirable due to the risks of skin and central nervous system complications and potential spread to unvaccinated contacts. [29][30][31] Such risks are particularly acute in adjuvant cancer immunotherapy protocols, where patients may be in an immunocompromised state because of their disease or primary therapy.…”

Section: Figure 7 Human DC Infected With Fowlpox Virus Retain Viabilimentioning

confidence: 99%

Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity

et al. 2000

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The identification of dendritic cells (DC) as the major antigen-presenting cell type of the immune system, combined with the development of procedures for their ex vivo culture, has opened possibilities for tumour immunotherapy based on the transfer of recombinant tumour antigens to DC. It is anticipated that the most effective type of response would be the stimulation of specific, MHC class I restricted cytotoxic T lymphocytes capable of recognising and destroying tumour cells. In order to make this approach possible, methods must be developed for the transfer of recombinant antigen to the DC in such a way that they will initiate an MHC class I restricted response. Here, we demonstrate that murine DC infected with a recombinant fowlpox virus (rFWPV) vector stimulate a powerful, MHC class I restricted response against a recombinant antigen. A rFWPV containing the OVA gene was constructed and used to infect the DC line

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Section: Figure 7 Human DC Infected With Fowlpox Virus Retain Viabilimentioning

confidence: 99%

Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity

et al. 2000

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“…13 Patients with colon cancer immunized with rCEA mounted a cytotoxic T lymphocyte (CTL) response against tumor cells loaded with CEA peptides. 14 Patients with colon cancer immunized with rCEA mounted both antibody and T-cell responses against CEA that were enhanced by adding granulocyte/macrophage-colony-stimulating factor (GM-CSF). 15 Unlike several infectious diseases, which are well controlled by humoral responses, solid tumors such as colon carcinoma are likely to require cellular responses for effect.…”

mentioning

confidence: 99%

Signal sequence deletion and fusion to tetanus toxoid epitope augment antitumor immune responses to a human carcinoembryonic antigen (CEA) plasmid DNA vaccine in a murine test system

et al. 2003

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Carcinoembryonic antigen (CEA, CEACAM5) is expressed on several human carcinomas including colon cancer. CEA contains signal peptides that target the protein through the endoplasmic reticulum and to the cell membrane. We constructed a plasmid DNA vaccine encoding a truncated CEA (DCEA), devoid of its signal peptides, and demonstrated that it was retained inside the cell, while full-length CEA (wtCEA) was expressed on the membrane. We hypothesized that intracellular retention of DCEA would enhance MHC class I presentation of CEA peptides, thus favoring cellular immune responses. In addition, a promiscuous T-helper epitope (Q830-L844 of tetanus toxoid) was fused to the N-terminal of the truncated CEA gene (tetDCEA). C57BL/6 mice immunized with DNA encoding wtCEA or tetDCEA developed both humoral and cellular immune responses to CEA. SCID mice transplanted with spleen cells from tetDCEA but not wtCEA-immunized C57BL/6 mice showed strong suppression of tumor growth after inoculation of human CEA-expressing colon carcinoma cells. Immune spleen cell populations depleted for either B, T or both B and T cells were active, indicating that effector cells might also reside in other populations. The present approach to manipulating antigen presentation may open new possibilities for immunotherapy against colon and other CEA-secreting carcinomas.

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“…There is as yet comparatively poor prediction of the relative immunogenicity of anti-idiotypes necessary for T-cell responsiveness in tumour systems (Raychaudhuri et al, 1990;Tsang et al, 1995). Recently, cytokines have been used in combination with monoclonal antibodies to enhance MHC (Rosa and Fellous, 1988) and CEA (Kantor et al, 1989) expression as well as to improve residual tumour radioimmunodetection .…”

Section: Designer Monoclonals Antiidiotypic Antibodies and Colorectmentioning

confidence: 99%

Biological therapy: approaches in colorectal cancer

Zbar

Lemoine²,

Wadhwa³

et al. 1998

Br J Cancer

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Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine

Abstract: These findings have implications in the development of specific second-generation cancer immunotherapy protocols.

Cited by 432 publications

References 0 publications

Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity

Dendritic cells infected with recombinant fowlpox virus vectors are potent and long-acting stimulators of transgene-specific class I restricted T lymphocyte activity

Signal sequence deletion and fusion to tetanus toxoid epitope augment antitumor immune responses to a human carcinoembryonic antigen (CEA) plasmid DNA vaccine in a murine test system

Biological therapy: approaches in colorectal cancer

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