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  • Review Article
  • Published:

Cancer vaccines: between the idea and the reality

Nature Reviews Immunology volume 3, pages 630–641 (2003)Cite this article

Key Points

  • Challenges facing all vaccines, including cancer vaccines, are outlined. The relative importance of the choice of antigen, choice of adjuvant and the type of elicited immunity is discussed.

  • The importance of using well-defined tumour antigens is emphasized and progress in their identification and characterization is reviewed.

  • Specific challenges facing cancer vaccines are outlined. The importance of age-induced changes in the immune system, tumour-induced immunosuppression, inefficient memory generation in the presence of chronic antigen and immune evasion is discussed.

  • Pre-clinical and clinical efforts in designing and testing therapeutic cancer vaccines are reviewed.

  • Prophylactic use of vaccines against viruses that are known to be aetiological causes of specific cancers is discussed.

  • A case is made for the prophylactic use of vaccines on the basis of shared, non-viral, tumour antigens.

Abstract

Whether vaccines are designed to prepare the immune system for the encounter with a pathogen or with cancer, certain common challenges need to be faced, such as what antigen and what adjuvant to use, what type of immune response to generate and how to make it long lasting. Cancer, additionally, presents several unique hurdles. Cancer vaccines must overcome immune suppression exerted by the tumour, by previous therapy or by the effects of advanced age of the patient. If used for cancer prevention, vaccines must elicit effective long-term memory without the potential of causing autoimmunity. This article addresses the common and the unique challenges to cancer vaccines and the progress that has been made in meeting them. Considering how refractory cancer has been to standard therapy, efforts to achieve immune control of this disease are well justified.

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Figure 1: A probable model of the evolution and fate of antitumour immune responses that develop coincidently with tumour growth.
Figure 2: Manipulation of antitumour immune responses by therapeutic vaccination.
Figure 3: Manipulation of antitumour immune responses by prophylactic vaccination.

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Acknowledgements

I thank former and present members of my laboratory, whose work has helped shaped my ideas. I also thank the National Institutes of Health, the American Cancer Society, the Susan G. Komen Foundation, the Nathan Arenson Fund for Pancreatic Cancer Research, and the Bob and Coleen Woeber Fund for Breast Cancer Research for support.

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Authors and Affiliations

  1. Department of Immunology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, E1040 Biomedical Science Tower, Pittsburgh, 15261, Pennsylvania, USA

    Olivera J. Finn

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DATABASES

LocusLink

4-1BB

CTLA4

cyclin B1

GM-CSF

HER2

IL-2

IL-4

IL-10

IL-12

IL-13

MAGE3

mucin 1

TGF-β

Entrez

HBV

HPV16

FURTHER INFORMATION

Vaccine tutorial

Cancer Research Institute

Therapeutic cancer vaccines

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Glossary

SHARED TUMOUR ANTIGENS

Molecules that are expressed by many tumours and not normal tissues, or expressed by normal tissue in a quantitatively and qualitatively different form.

UNIQUE TUMOUR ANTIGENS

Products of random mutations or gene rearrangements, often induced by physical or chemical carcinogens, and therefore expressed uniquely by individual tumours.

EPITOPE SPREADING

A term originally applied to responses to autoantigens that tend to become more diverse as the response persists. This phenomenon is also known as determinant spreading or antigen spreading. In the setting of a vaccine, it refers to responses that are generated to antigens other than those contained in the vaccine.

ADJUVANT

An agent mixed with an antigen that enhances the immune response to that antigen after immunization.

T HELPER 1/2 CELLS

TH1/TH2 cells. Two subsets of activated CD4+ T cells that can be distinguished by the cytokines they produce. TH1 cells produce interferon-γ, lymphotoxin and tumour-necrosis factor, and enhance cell-mediated immunity. TH2 cells produce interleukin-4 (IL-4), IL-5 and IL-13, and support humoral immunity.

IDIOTYPE

The unique portion of either a T-cell receptor or an immunoglobulin molecule, defined by the hypervariable regions and involved in antigen recognition.

ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY

(ADCC). Killing of antibody-coated target cells by cells expressing Fc receptors (FcRs) that recognize the constant region of the bound antibody. Most ADCC is mediated by natural killer cells that express the FcR CD16 or FcγRIII on their cell surface.

DELAYED-TYPE HYPERSENSITIVITY

(DTH). A cellular immune response to antigen injected into the skin that develops over 24–72 hours with the infiltration of T cells and monocytes, and depends on the production of T helper 1-specific cytokines.

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Finn, O. Cancer vaccines: between the idea and the reality. Nat Rev Immunol 3, 630–641 (2003). https://doi.org/10.1038/nri1150

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