SupplementClinical promise of tumour immunology
Section snippets
Antigens recognised by lymphocytes
Lymphocytes kill cells that display appropriate targets.4 CD8 T-cells are critical mediators of this response although CD4 cells help by secreting cytokines. The clinical challenge is to harness this system, which is so effective for the removal of virally infected cells and other foreign cells, such as allografts, for cancer rejection.
Intracellular protein targets for immunotherapy include viral antigens and mutated proteins (panel). Newer targets are the MAGE family of proteins, BAGE, GAGE,5
Vaccines
Native antitumour immunity fails because tumour antigens are not sufficiently immunogenic or because antigen-negative cells emerge. Adjuvants will be required to make immunisation against tumour antigens more effective. Options include emulsions (eg, MF59), bacterial products (eg, Detox), saponins (eg, QS-21), and immunostimulatory complexes. Antigens can also be conjugated to carriers such as keynote limpet haemocyanin or mannan. Cytokines such as granulocyte-macrophage colony-stimulating
Cancer vaccines
In melanoma, vaccination with the ganglioside GM2 tended to increase survival,26 and further studies are planned. Results from trials that have targeted peptide epitopes recognised by T-cells are preliminary but encouraging.8, 17, 21 Not surprisingly, the addition of cytokines such as GM-CSF enhances immune responses,17 Tumour escape from immune control has emerged; however, tools are available to evaluate this phenomenon and to develop strategies to overcome it. Improved methods for
Conclusions
Considerable excitement has greeted the era of antibody engineering and of the structurally defined tumour antigen. The tools for analysing antigen-targeting strategies and human immune responses to cancer antigens, and the potential for a more rigorous scientific basis for cancer immunotherapy, are now available. Our understanding is catching up with expectations. While not underestimating the challenges, the new clinical opportunities that are offered by vaccine and antibody therapies point
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