Cancer Vaccines (Fact Sheet)

Can cancer treatment vaccines be combined with other types of cancer therapy?

Yes. In many of the clinical trials of cancer treatment vaccines that are now under way, vaccines are being given with other forms of cancer therapy. Therapies that have been combined with cancer treatment vaccines include surgery, chemotherapy, radiation therapy, and some forms of targeted therapy, including therapies that are intended to boost immune system responses against cancer.

Several studies have suggested that cancer treatment vaccines may be most effective when given in combination with other forms of cancer therapy (21, 25). In addition, in some clinical trials, cancer treatment vaccines have appeared to increase the effectiveness of other cancer therapies (21, 25).

Additional evidence suggests that surgical removal of large tumors may enhance the effectiveness of cancer treatment vaccines (25). In patients with extensive disease, the immune system may be overwhelmed by the cancer. Surgical removal of the tumor may make it easier for the body to develop an effective immune response.

Researchers are also designing clinical trials to answer questions such as whether a specific cancer treatment vaccine works best when it is administered before chemotherapy, after chemotherapy, or at the same time as chemotherapy. Answers to such questions may not only provide information about how best to use a specific cancer treatment vaccine but also reveal additional basic principles to guide the future development of combination therapies involving vaccines.

What additional research is under way?

Although researchers have identified many cancer-associated antigens, these molecules vary widely in their capacity to stimulate a strong anticancer immune response. Two major areas of research aimed at developing better cancer treatment vaccines involve the identification of novel cancer-associated antigens that may prove more effective in stimulating immune responses than the already known antigens and the development of methods to enhance the ability of cancer-associated antigens to stimulate the immune system. Research is also under way to determine how to combine multiple antigens within a single cancer treatment vaccine to produce optimal anticancer immune responses (26). 

Perhaps the most promising avenue of cancer vaccine research is aimed at better understanding the basic biology underlying how immune system cells and cancer cells interact. New technologies are being created as part of this effort. For example, a new type of imaging technology allows researchers to observe killer T cells and cancer cells interacting inside the body (27).

Researchers are also trying to identify the mechanisms by which cancer cells evade or suppress anticancer immune responses. A better understanding of how cancer cells manipulate the immune system could lead to the development of new drugs that block those processes and thereby improve the effectiveness of cancer treatment vaccines (28). For example, some cancer cells produce chemical signals that attract white blood cells known as regulatory T cells, or Tregs, to a tumor site. Tregs often release cytokines that suppress the activity of nearby killer T cells (21, 29). The combination of a cancer treatment vaccine with a drug that would block the negative effects of one or more of these suppressive cytokines on killer T cells might improve the vaccine’s effectiveness in generating potent killer T cell antitumor responses.

Selected References

1. Pardoll DM. Cancer immunology. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, editors. Abeloff’s Clinical Oncology. 4th ed. Philadelphia: Churchill Livingstone, 2008.

2. Murphy KM, Travers P, Walport M, editors. Janeway’s Immunobiology. 7th ed. New York: Garland Science, 2007.

3. Waldmann TA. Effective cancer therapy through immunomodulation. Annual Review of Medicine 2006;  57:65–81.

4. Emens LA. Cancer vaccines: on the threshold of success. Expert Opinion on Emerging Drugs 2008; 13(2):295–308.

5. Sioud M. An overview of the immune system and technical advances in tumor antigen discovery and validation. Methods in Molecular Biology 2007; 360:277–318.

6. Pazdur MP, Jones JL. Vaccines: an innovative approach to treating cancer. Journal of Infusion Nursing 2007; 30(3):173–178.

7. Lollini PL, Cavallo F, Nanni P, Forni G. Vaccines for tumour prevention. Nature Reviews Cancer 2006; 6(3):204–216.

8. Frazer IH, Lowy DR, Schiller JT. Prevention of cancer through immunization: prospects and challenges for the 21st century. European Journal of Immunology 2007; 37(Suppl 1):S148–S155.

9. Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clinical Science 2006; 110(5):525–541.

10. Parkin DM. The global health burden of infection-associated cancers in the year 2002. International Journal of Cancer 2006; 118(12):3030–3044.

11. Lowy DR, Schiller JT. Prophylactic human papillomavirus vaccines. Journal of Clinical Investigation 2006; 116(5):1167–1173.

12. U.S. Centers for Disease Control and Prevention. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) Part 1: immunization of infants, children, and adolescents. Morbidity and Mortality Weekly Report 2005; 54(No. RR–16):1–31.

13. Mueller NE. Cancers caused by infections: unequal burdens. Cancer Epidemiology, Biomarkers & Prevention 2003; 12(3):237s.

14. International Agency for Research on Cancer (2011). Agents Classified by the IARC Monographs Exit Disclaimer, Volumes 1–100. Retrieved November 15, 2011.

15. Rivoltini L, Canese P, Huber V, et al. Escape strategies and reasons for failure in the interaction between tumour cells and the immune system: how can we tilt the balance towards immune-mediated cancer control? Expert Opinion on Biological Therapy 2005; 5(4):463–476.

16. Rosenberg SA, Yang JC, Restifo NP. Cancer immunotherapy: moving beyond current vaccines. Nature Medicine 2004; 10(9):909–915.

17. Renkvist N, Castelli C, Robbins PF, Parmiani G. A listing of human tumor antigens recognized by T cells. Cancer Immunology and Immunotherapy 2001; 50(1):3–15.

18. Parmiani G, Russo V, Marrari A, et al. Universal and stemness-related tumor antigens: potential use in cancer immunotherapy. Clinical Cancer Research 2007; 13(19):5675–5679.

19. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New England Journal of Medicine 2010; 363(5):411–422.

20. Parmiani G, De Filippo A, Novellino L, Castelli C. Unique human tumor antigens: immunobiology and use in clinical trials. The Journal of Immunology 2007; 178(4):1975–1979.

21. Finn OJ. Cancer immunology. The New England Journal of Medicine 2008; 358(25):2704–2715.

22. Curigliano G, Spitaleri G, Dettori M, et al. Vaccine immunotherapy in breast cancer treatment: promising, but still early. Expert Review of Anticancer Therapy 2007; 7(9):1225–1241.

23. Chiarella P, Massi E, De Robertis M, Signori E, Fazio VM. Adjuvants in vaccines and for immunisation: current trends. Expert Opinion on Biological Therapy 2007; 7(10):1551–1562.

24. Herr HW, Morales A. History of Bacillus Calmette-Guérin and bladder cancer: an immunotherapy success story. The Journal of Urology 2008; 179(1):53–56.

25. Emens LA. Chemotherapy and tumor immunity: an unexpected collaboration. Frontiers in Bioscience 2008; 13:249–257.

26. Schlom J, Arlen PM, Gulley JL. Cancer vaccines: moving beyond current paradigms. Clinical Cancer Research 2007; 13(13):3776–3782.

27. Ng LG, Mrass P, Kinjyo I, Reiner SL, Weninger W. Two-photon imaging of effector T-cell behavior: lessons from a tumor model. Immunological Reviews 2008; 221:147–162.

28. Garnett CT, Greiner JW, Tsang KY, et al. TRICOM vector based cancer vaccines. Current Pharmaceutical Design 2006; 12(3):351–361.

29. Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nature Reviews Immunology 2006; 6(4):295–307.

Source: National Cancer Institute