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Cancer immunity and clinical oncology 

Cancer immunity and clinical oncology

Chapter:
Cancer immunity and clinical oncology
Author(s):

Maries van den Broek

, Lotta von Boehmer

, Kunle Odunsi

, and Alexander Knuth

DOI:
10.1093/med/9780199204854.003.0604

May 30, 2013: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

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date: 28 April 2017

Patients develop immune-mediated defence mechanisms against cancers, which are referred to as the ‘three E’s’: (1) elimination—corresponding to immunological control of the tumour or immunosurveillance; (2) equilibrium—the process by which the immune response iteratively selects/promotes less immunogenic tumour variants; and (3) escape—when the immunologically sculptured tumour expands in an uncontrolled manner.

Human cancer antigens

These represent proteins that are uniquely (over)expressed in malignant tissues and function as target for immunotherapy. They can be divided in following categories: (1) cancer–testis (CT) antigens—silent in healthy tissues, except germ cells, but expressed in various cancer types (e.g. NY-ESO-1, which is probably the most immunogenic CT antigen known); (2) differentiation antigens of certain cell types, such as melanocytes or breast cell epithelia; (3) unique tumour-specific antigens that are the products of genetic alterations; (4) virus-encoded antigens in virus-associated cancers; (5) ubiquitous antigens that are overexpressed in tumours.

Cancer immunotherapy

Antigen-specific immunotherapy in cancer patients focuses either on (1) T-cell-mediated approaches or on (2) antibodies. T cells are generally directed against endogenous tumour-derived proteins that are processed and presented in the context of major histocompatibility complex molecules, whereas antibodies are directed at molecular targets expressed at the cancer cell surface.

Monoclonal antibodies—these are now established and integrated in many treatment regimens in cancer medicine, e.g. rituximab (targeting CD20) in non-Hodgkin’s lymphoma and trastuzumab (targeting Erb2/HER2) in breast cancer).

Cancer vaccination—the keys to efficient vaccination are (1) availability of an immunogenic, tumour-associated antigen; (2) a route, schedule, and packaging of the antigen that will induce an optimal immune response in vivo; (3) the combination of antigen with an adjuvant to support the induction of a strong immune response in vivo; (4) sustained immunity; and (5) inhibition of regulatory pathways, such as CTLA-4, PD-1, and Tregs.

At this early stage of development, cancer immunotherapy should be offered only in the context of carefully monitored clinical trials conducted by experienced clinical research teams.

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