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  • Review Article
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Identification of tumour-associated t-cell epitopes for vaccine development

Nature Reviews Cancer volume 2, page 514 (2002)Cite this article

Key Points

  • T-cell epitopes from tumour antigens have been included in many vaccination studies, and their potential to induce antitumour immune responses has become manifest. Nevertheless, the clinical outcome of such studies has to be improved.

  • The number of known epitopes is still limited; therefore, some tumours cannot be treated by immunotherapeutic approaches. For others, the efficacy is not yet optimal.

  • T-cell epitopes from tumour antigens can be defined by two principal strategies: one starts from an existing T-cell response and identifies the target of the response, whereas the other uses the sequence of a tumour antigen and employs epitope prediction to identify the relevant epitopes.

  • New tumour antigens can be discovered by analysing the specificity of existing T-cell responses, or by screening strategies such as the SEREX programme, comparative proteome analysis or gene-expression profiling.

  • To improve the clinical outcome of antitumour vaccinations, tumour-escape mechanisms have to be avoided by the use of efficient, multitarget vaccines.

  • With the growing number of T-cell epitopes, it will become feasible to design patient-specific, individual vaccines that address several different antigens from one tumour and several HLA specificities, including class-II-restricted epitopes.

Abstract

Ten years ago, the first melanoma patient was successfully treated by vaccination with a short peptide, which was, in fact, the first tumour-specific T-cell epitope ever defined — MAGE. Since then, a number of clinical vaccination studies have underlined the potential of tumour-specific T-cell epitopes. But, how can we identify more epitopes to improve their efficacy as an anticancer treatment?

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Figure 1: Strategies for the characterization of T-cell epitopes.
Figure 2: Complementary information leads to the identification of useful tumour epitopes.

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Author information

Authors and Affiliations

  1. Department of Immunology, University of Tübingen, Institute for Cell Biology, Auf der Morgenstelle 15, Tübingen, D-72076, Germany

    Stefan Stevanovic

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  1. Stefan Stevanovic
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DATABASES

Cancer.gov

breast cancer

cervical cancer

gastrointestinal cancer

Kaposi's sarcoma

kidney cancer

lung cancer

melanoma

non-Hodgkin's lymphoma

ovarian cancer

pancreatic cancer

prostate cancer

thyroid cancer

LocusLink

CD4

CD8

ERBB2

MAGE1

p53

RAS

survivin

telomerase

Medscape DrugInfo

Herceptin

FURTHER INFORMATION

Cancer trials

MHC binding prediction BIMAS

Proteasomal cleavage prediction NetChop

Proteasomal cleavage prediction PAPROC

SEREX database

SYFPEITHI database

Glossary

HLAs

Human leukocyte antigens, which are molecules of the human major histocompatibility complex.

CD8

A surface molecule that is expressed exclusively by cytotoxic T cells.

CD4

A surface molecule that is expressed exclusively by T-helper cells.

MHC CLASS II MOLECULES

Peptide receptors, similar to class I molecules in structure and function, but exclusively expressed by a small set of immune cells. They mainly present peptides from extracellular proteins to T-helper cells.

CYTOTOXIC T LYMPHOCYTES

(CTLs: killer cells, cytotoxic T cells). These control all major histocompatibility complex class-I-expressing body cells for the presence of abnormal (viral, tumour-associated) peptides.

MHC CLASS I MOLECULES

Highly polymorphic glycoproteins that are expressed by every nucleated body cell of vertebrates, and that are encoded by the gene cluster 'major histocompatibility complex' (MHC). The human MHC molecules are termed HLA (human leukocyte antigen) molecules. MHC class I molecules mainly present peptides from intracellular proteins to cytotoxic T cells.

DENDRITIC CELLS

(DCs). These present T-cell epitopes very efficiently and are able to activate cytotoxic T lymphocytes.

MELANOMA

Skin cancer, originating from transformed melanocytes.

MAGE

Melanoma antigen; a family of proteins that are expressed only in testis or tumour cells.

PROTEOMICS

Analysis of the entirety of proteins from a tissue sample, separated by two-dimensional gel electrophoresis. Each individual protein spot can be identified after tryptic digestion and mass spectrometrical analysis of the resulting peptides.

MICROARRAY ANALYSIS

'DNA chips' contain many thousands of oligonucleotides that represent fragments of genes, immobilized on a solid surface. They are probed with cDNA that is prepared from mRNA of tissue samples and so give quantitative information about gene expression.

MELANOSOMES

Subcellular organelles in melanocytes, which contain the skin's pigments.

PERIPHERAL-BLOOD MONONUCLEAR CELLS

(PBMCs). Includes B cells, T cells and monocytes. These can be obtained from whole blood after ficoll density-gradient centrifugation.

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Stevanovic, S. Identification of tumour-associated t-cell epitopes for vaccine development. Nat Rev Cancer 2, 514 (2002). https://doi.org/10.1038/nrc841

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