Adjuvants and the promotion of Th1-type cytokines in tumour immunotherapy.
Immunotherapy includes both active and passive mechanisms that have the potential to treat many tumour types. Whereas monoclonal antibodies may kill cells by merely binding to them, 'cancer vaccines' involve the induction of an active immune response. The activation of tumour antigen-specific T-helper and cytotoxic T lymphocytes or non-specific macrophages and natural killer (NK) cells using immunotherapeutic approaches may lead to the subsequent destruction of tumour tissue. Administration of a tumour antigen alone is often not sufficient to stimulate an appropriate immune response. However, incorporating an immunological adjuvant into a vaccine regime often improves anti-tumour immunity. There are various types of adjuvants used in immunotherapy, ranging from microbial, chemical, and cellular components to proteins and cytokines. Previous reports have demonstrated that the induction of Th1-promoting cytokines, using specific adjuvants, can enhance anti-tumour immunity and can reduce or even prevent tumour growth. There is also increasing evidence that many adjuvants induce Th1-type cytokines, which correlates with the induction anti-tumour immunity. Th1-type responses which comprise cell-mediated immunity are characterised by the secretion of interferon-gamma by T cells, which is induced by antigen-presenting cell (APC)-derived IL-12. This review describes immunoadjuvants that are currently undergoing preclinical investigation, and emerging clinical data revealing that adjuvants which induce Th1-type responses can improve the efficacy of cancer vaccines. Therefore, the use of Th1-inducing adjuvants may provide an essential strategy for the future success of immunotherapy.
Dredge
Keith
K
Division of Oncology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, U.K. k.dredge@sghms.ac.uk
Marriott
J Blake
JB
Todryk
Stephen M
SM
Dalgleish
Angus G
AG
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D019496:Cancer Vaccines; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D018417:Th1 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines