TRICOM vector based cancer vaccines

Charlie T. Garnett, John W. Greiner, Kwong Yok Tsang, Chie Kudo-Saito, Douglas W. Grosenbach, Mala Chakraborty, James L. Gulley, Philip M. Arlen, Jeffrey Schlom, James W. Hodge

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

For the immune system to mount an effective antitumor T-cell response, an adequate number of T-cells specific for the antigens expressed by the malignancy must be activated [1]. Since most antigens expressed by tumors are "self"-antigens, tumor antigens often lack endogenous immunogenicity and thus do not sufficiently activate T-cells to levels that can mediate tumor eradication. In addition, virtually all solid tumor cells lack the costimulatory molecules necessary to activate tumor-specific T-cells. Approaches that stimulate immune responses to these tumor antigens have the potential to alter this poor responsiveness. This theory has promoted the use of active immunotherapy to generate immune responses against tumor-associated antigens (TAAs) for the treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as delivery vehicles for TAAs in combination with T-cell costimulatory molecules. Initial studies have demonstrated that the insertion of costimulatory molecule trangenes into viral vectors, along with a TAA transgene, greatly enhances the immune response to the antigen. Using this approach, a TRIad of COstimulatory Molecules (TRICOM; B7-1, ICAM-1 and LFA-3) has been shown to enhance T-cell responses to TAAs to levels far greater than any one or two of the costimulatory molecules in combination. In this article, preclinical findings and recent clinical applications of TRICOM-based vaccines as a cancer immunotherapy are reviewed.

Original languageEnglish
Pages (from-to)351-361
Number of pages11
JournalCurrent Pharmaceutical Design
Volume12
Issue number3
DOIs
Publication statusPublished - 2006 Jan
Externally publishedYes

Fingerprint

Cancer Vaccines
Neoplasm Antigens
T-Lymphocytes
Neoplasms
Vaccines
CD80 Antigens
CD58 Antigens
Poxviridae
Antigens
Active Immunotherapy
Second Primary Neoplasms
Histocompatibility Antigens Class II
Autoantigens
Intercellular Adhesion Molecule-1
Transgenes
Immunotherapy
Immune System

Keywords

  • Cancer immunotherapy
  • Costimulation
  • TAA
  • TRICOM
  • Vaccination

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Garnett, C. T., Greiner, J. W., Tsang, K. Y., Kudo-Saito, C., Grosenbach, D. W., Chakraborty, M., ... Hodge, J. W. (2006). TRICOM vector based cancer vaccines. Current Pharmaceutical Design, 12(3), 351-361. https://doi.org/10.2174/138161206775201929

TRICOM vector based cancer vaccines. / Garnett, Charlie T.; Greiner, John W.; Tsang, Kwong Yok; Kudo-Saito, Chie; Grosenbach, Douglas W.; Chakraborty, Mala; Gulley, James L.; Arlen, Philip M.; Schlom, Jeffrey; Hodge, James W.

In: Current Pharmaceutical Design, Vol. 12, No. 3, 01.2006, p. 351-361.

Research output: Contribution to journalArticle

Garnett, CT, Greiner, JW, Tsang, KY, Kudo-Saito, C, Grosenbach, DW, Chakraborty, M, Gulley, JL, Arlen, PM, Schlom, J & Hodge, JW 2006, 'TRICOM vector based cancer vaccines', Current Pharmaceutical Design, vol. 12, no. 3, pp. 351-361. https://doi.org/10.2174/138161206775201929
Garnett CT, Greiner JW, Tsang KY, Kudo-Saito C, Grosenbach DW, Chakraborty M et al. TRICOM vector based cancer vaccines. Current Pharmaceutical Design. 2006 Jan;12(3):351-361. https://doi.org/10.2174/138161206775201929
Garnett, Charlie T. ; Greiner, John W. ; Tsang, Kwong Yok ; Kudo-Saito, Chie ; Grosenbach, Douglas W. ; Chakraborty, Mala ; Gulley, James L. ; Arlen, Philip M. ; Schlom, Jeffrey ; Hodge, James W. / TRICOM vector based cancer vaccines. In: Current Pharmaceutical Design. 2006 ; Vol. 12, No. 3. pp. 351-361.
@article{de6f238d4e6548a8b7894a54ef040ba7,
title = "TRICOM vector based cancer vaccines",
abstract = "For the immune system to mount an effective antitumor T-cell response, an adequate number of T-cells specific for the antigens expressed by the malignancy must be activated [1]. Since most antigens expressed by tumors are {"}self{"}-antigens, tumor antigens often lack endogenous immunogenicity and thus do not sufficiently activate T-cells to levels that can mediate tumor eradication. In addition, virtually all solid tumor cells lack the costimulatory molecules necessary to activate tumor-specific T-cells. Approaches that stimulate immune responses to these tumor antigens have the potential to alter this poor responsiveness. This theory has promoted the use of active immunotherapy to generate immune responses against tumor-associated antigens (TAAs) for the treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as delivery vehicles for TAAs in combination with T-cell costimulatory molecules. Initial studies have demonstrated that the insertion of costimulatory molecule trangenes into viral vectors, along with a TAA transgene, greatly enhances the immune response to the antigen. Using this approach, a TRIad of COstimulatory Molecules (TRICOM; B7-1, ICAM-1 and LFA-3) has been shown to enhance T-cell responses to TAAs to levels far greater than any one or two of the costimulatory molecules in combination. In this article, preclinical findings and recent clinical applications of TRICOM-based vaccines as a cancer immunotherapy are reviewed.",
keywords = "Cancer immunotherapy, Costimulation, TAA, TRICOM, Vaccination",
author = "Garnett, {Charlie T.} and Greiner, {John W.} and Tsang, {Kwong Yok} and Chie Kudo-Saito and Grosenbach, {Douglas W.} and Mala Chakraborty and Gulley, {James L.} and Arlen, {Philip M.} and Jeffrey Schlom and Hodge, {James W.}",
year = "2006",
month = "1",
doi = "10.2174/138161206775201929",
language = "English",
volume = "12",
pages = "351--361",
journal = "Current Pharmaceutical Design",
issn = "1381-6128",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - TRICOM vector based cancer vaccines

AU - Garnett, Charlie T.

AU - Greiner, John W.

AU - Tsang, Kwong Yok

AU - Kudo-Saito, Chie

AU - Grosenbach, Douglas W.

AU - Chakraborty, Mala

AU - Gulley, James L.

AU - Arlen, Philip M.

AU - Schlom, Jeffrey

AU - Hodge, James W.

PY - 2006/1

Y1 - 2006/1

N2 - For the immune system to mount an effective antitumor T-cell response, an adequate number of T-cells specific for the antigens expressed by the malignancy must be activated [1]. Since most antigens expressed by tumors are "self"-antigens, tumor antigens often lack endogenous immunogenicity and thus do not sufficiently activate T-cells to levels that can mediate tumor eradication. In addition, virtually all solid tumor cells lack the costimulatory molecules necessary to activate tumor-specific T-cells. Approaches that stimulate immune responses to these tumor antigens have the potential to alter this poor responsiveness. This theory has promoted the use of active immunotherapy to generate immune responses against tumor-associated antigens (TAAs) for the treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as delivery vehicles for TAAs in combination with T-cell costimulatory molecules. Initial studies have demonstrated that the insertion of costimulatory molecule trangenes into viral vectors, along with a TAA transgene, greatly enhances the immune response to the antigen. Using this approach, a TRIad of COstimulatory Molecules (TRICOM; B7-1, ICAM-1 and LFA-3) has been shown to enhance T-cell responses to TAAs to levels far greater than any one or two of the costimulatory molecules in combination. In this article, preclinical findings and recent clinical applications of TRICOM-based vaccines as a cancer immunotherapy are reviewed.

AB - For the immune system to mount an effective antitumor T-cell response, an adequate number of T-cells specific for the antigens expressed by the malignancy must be activated [1]. Since most antigens expressed by tumors are "self"-antigens, tumor antigens often lack endogenous immunogenicity and thus do not sufficiently activate T-cells to levels that can mediate tumor eradication. In addition, virtually all solid tumor cells lack the costimulatory molecules necessary to activate tumor-specific T-cells. Approaches that stimulate immune responses to these tumor antigens have the potential to alter this poor responsiveness. This theory has promoted the use of active immunotherapy to generate immune responses against tumor-associated antigens (TAAs) for the treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as delivery vehicles for TAAs in combination with T-cell costimulatory molecules. Initial studies have demonstrated that the insertion of costimulatory molecule trangenes into viral vectors, along with a TAA transgene, greatly enhances the immune response to the antigen. Using this approach, a TRIad of COstimulatory Molecules (TRICOM; B7-1, ICAM-1 and LFA-3) has been shown to enhance T-cell responses to TAAs to levels far greater than any one or two of the costimulatory molecules in combination. In this article, preclinical findings and recent clinical applications of TRICOM-based vaccines as a cancer immunotherapy are reviewed.

KW - Cancer immunotherapy

KW - Costimulation

KW - TAA

KW - TRICOM

KW - Vaccination

UR - http://www.scopus.com/inward/record.url?scp=33644872328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33644872328&partnerID=8YFLogxK

U2 - 10.2174/138161206775201929

DO - 10.2174/138161206775201929

M3 - Article

VL - 12

SP - 351

EP - 361

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 3

ER -