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Review
. 2009 Feb 21;373(9664):673-83.
doi: 10.1016/S0140-6736(09)60404-9.

Use of tumour-responsive T cells as cancer treatment

Mary L Disis  1 , Helga Bernhard, Elizabeth M Jaffee
Affiliations
Review

Use of tumour-responsive T cells as cancer treatment

Mary L Disis et al. Lancet. .

Abstract

The stimulation of a tumour-specific T-cell response has several theoretical advantages over other forms of cancer treatment. First, T cells can home in to antigen-expressing tumour deposits no matter where they are located in the body-even in deep tissue beds. Additionally, T cells can continue to proliferate in response to immunogenic proteins expressed in cancer until all the tumour cells are eradicated. Finally, immunological memory can be generated, allowing for eradication of antigen-bearing tumours if they reoccur. We will highlight two direct methods of stimulating tumour-specific T-cell immunity: active immunisation with cancer vaccines and infusion of competent T cells via adoptive T-cell treatment. Preclinical and clinical studies have shown that modulation of the tumour microenvironment to support the immune response is as important as stimulation of the most appropriate effector T cells. The future of T-cell immunity stimulation to treat cancer will need combination approaches focused on both the tumour and the T cell.

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Conflict of interest statement

Conflict of interest statement

MLD is an inventor on patents held by the University of Washington pertaining to T-cell therapies. EMJ has been a consultant for Amplimmune, where she provides advice on new agent development (pre-clinical advice to date); has been a consultant for Bristol-Myers Squibb in the past year; has licensed intellectual property to Anza Corp and has the potential to receive royalties in the future; and although she does not receive any financial support or has the potential for royalties, John Hopkins has the potential to receive royalties from Cell Geneys on the GVAX vaccine in the future. HB declares that she has no conflict of interest.

Figures

Figure 1
Figure 1. Tumour vaccine cells genetically modified to produce danger stimuli (similar to granulocyte-macrophage colony-stimulating factor) to attract and mature antigen-presenting cells
Tumour-associated antigens are shed from dying vaccine cells to provide a source of antigen. Antigens can then be taken up by antigen-presenting cells, expressing co-stimulatory molecules such as B7-1, to be processed and presented to T cells. Phenotypes of CD4+ T cells can either enhance (eg, Th1) or inhibit (eg, Treg) the immune response.
Figure 2
Figure 2. Isolation and ex-vivo stimulation of antigen-specific tumour-reactive T lymphocytes for adoptive transfer
Autologous lymphocytes are stimulated ex vivo with antigen-loaded antigen-presenting cells, such as dendritic cells. Enriched tumour-specific T cells are then re-infused for treatment.
See this image and copyright information in PMC

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