Challenges Facing the Development of Cancer Vaccines

  • Mayer Fishman
Part of the Methods in Molecular Biology book series (MIMB, volume 1139)


Just like any other effective immunization in medicine, cancer vaccines need to have antigens with particular specificity and immunostimulatory features, the immune responses to be elicited in the body, and therapeutic effect—regression or prevention of the cancer—must be meaningful and clinically observable. There are many choices for cancer antigens, such as tissue-specific proteins, cancer-specific proteins, class I- or class II-restricted peptides derived from those, or in situ and whole-cell-derived products are some examples. Another translational issue is that cancer patients are heterogeneous with respect to the extent to which the immune system is already activated with potential to impact the tumor growth or, conversely, the extent to which the immune system has been impaired through a prior and ongoing interaction with the tumor. Conventional or immunologic tests have potential to define a subset of patients with better chance or response, so that particular vaccines can be tested. Treatment of cancer patients is expensive, and trials are slow. To meet these challenges in practical terms will require not only careful scientific technical work for product development, coordination with clinicians to define patient subsets with diseases that can show responses, but also a comprehensive, practical implementation so that we can unlock the full potential of anticancer vaccines.

Key words

Cancer vaccines Tumor antigens Antigen presentation 


  1. 1.
    Palucka K et al (2001) Dendritic cells and immunity against cancer. J Intern Med 269(1):64–73CrossRefGoogle Scholar
  2. 2.
    Janikashvili N et al (2011) The dendritic cell-regulatory T lymphocyte crosstalk contributes to tumor-induced tolerance. Clin Dev Immunol 430394. Epub 2011 Nov 3Google Scholar
  3. 3.
    Gerlinger M et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366(10):883–892PubMedCrossRefGoogle Scholar
  4. 4.
    Frankel TL et al (2010) Both CD4 and CD8 T cells mediate equally effective in vivo tumor treatment when engineered with a highly avid TCR targeting tyrosinase. J Immunol 184(11):5988–5998PubMedCrossRefGoogle Scholar
  5. 5.
    Dalerba P et al (1998) High homogeneity of MAGE, BAGE, GAGE, tyrosinase and Melan-A/MART-1 gene expression in clusters of multiple simultaneous metastases of human melanoma: implications for protocol design of therapeutic antigen-specific vaccination strategies. Int J Cancer 77(2):200–204PubMedCrossRefGoogle Scholar
  6. 6.
    Iwami K et al (2012) Peptide-pulsed dendritic cell vaccination targeting interleukin-13 receptor α2 chain in recurrent malignant glioma patients with HLA-A*24/A*02 allele. Cytotherapy 14(6):733–742PubMedCrossRefGoogle Scholar
  7. 7.
    Shimato S et al (2008) Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor alpha2 chain, a glioma-associated antigen. J Neurosurg 109(1):117–122PubMedCrossRefGoogle Scholar
  8. 8.
    Fishman M (2009) A changing world for DCvax: a PSMA loaded autologous dendritic cell vaccine for prostate cancer. Expert Opin Biol Ther 9(12):1565–1575PubMedCrossRefGoogle Scholar
  9. 9.
    Slota M et al (2011) ELISpot for measuring human immune responses to vaccines. Expert Rev Vaccines 10(3):299–306PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Reiman JM et al (2007) Tumor immunoediting and immunosculpting pathways to cancer progression. Semin Cancer Biol 17(4):275–287PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Kim R et al (2007) Cancer immunoediting from immune surveillance to immune escape. Immunology 121(1):1–14PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Tarp MA, Clausen H (2008) Mucin-type O-glycosylation and its potential use in drug and vaccine development. Biochim Biophys Acta 1780(3):546–563PubMedCrossRefGoogle Scholar
  13. 13.
    Saldova R et al (2011) Core fucosylation and alpha2-3 sialylation in serum N-glycome is significantly increased in prostate cancer comparing to benign prostate hyperplasia. Glycobiology 21(2):195–205PubMedCrossRefGoogle Scholar
  14. 14.
    Schuster SJ et al (2011) Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. J Clin Oncol 29(20):2787–2794PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Wood C, C-100-12 RCC Study Group et al (2008) An adjuvant autologous therapeutic vaccine (HSPPC-96; vitespen) versus observation alone for patients at high risk of recurrence after nephrectomy for renal cell carcinoma: a multicentre, open-label, randomised phase III trial. Lancet 372(9633):145–154PubMedCrossRefGoogle Scholar
  16. 16.
    Jocham D et al (2004) Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomised controlled trial. Lancet 363(9409):594–599PubMedCrossRefGoogle Scholar
  17. 17.
    Fishman M et al (2008) Phase II trial of B7-1 (CD-86) transduced, cultured autologous tumor cell vaccine plus subcutaneous interleukin-2 for treatment of stage IV renal cell carcinoma. J Immunother 1:72–80CrossRefGoogle Scholar
  18. 18.
    Kantoff PW et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363(5):411–422PubMedCrossRefGoogle Scholar
  19. 19.
    Nagaraj S et al (2007) Dendritic cell-based full-length survivin vaccine in treatment of experimental tumors. J Immunother 30(2):169–179PubMedCrossRefGoogle Scholar
  20. 20.
    Pendino F et al (2006) Telomeres and telomerase: pharmacological targets for new anticancer strategies? Curr Cancer Drug Targets 6(2):147–180PubMedCrossRefGoogle Scholar
  21. 21.
    Lane DP et al (2010) p53-based cancer therapy. Cold Spring Harb Perspect Biol 2(9):a001222, Epub May 12PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Burt C et al (2013) HLA-A, -B, -DR allele group frequencies in 7007 kidney transplant list patients in 27 UK centres. Int J Immunogenet 2013 Jun;40(3):209–215Google Scholar
  23. 23.
    Mack SJ et al (2009) HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies distinguish Eastern European Americans from the general European American population. Tissue Antigens 73(1):17–32PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    de Gruijl TD et al (2008) Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines. Cancer Immunol Immunother 57(10):1569–1577PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Le DT et al (2010) Cellular vaccine approaches. Cancer J 16(4):304–310PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Facciabene A et al (2012) T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res 72(9):2162–2171PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    So EY, Ouchi T (2010) The application of Toll like receptors for cancer therapy. Int J Biol Sci 6(7):675–681PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Chiang CL et al (2011) Adjuvants for enhancing the immunogenicity of whole tumor cell vaccines. Int Rev Immunol 30(2–3):150–182PubMedCrossRefGoogle Scholar
  29. 29.
    Kusmartsev S, Gabrilovich DI (2002) Immature myeloid cells and cancer-associated immune suppression. Cancer Immunol Immunother 51(6):293–298PubMedCrossRefGoogle Scholar
  30. 30.
    Gabrilovich DI et al (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12(4):253–268PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Ruffell B et al (2012) Differential macrophage programming in the tumor microenvironment. Trends Immunol 33(3):119–126, Epub 2012 Jan 23PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Mayer Fishman
    • 1
  1. 1.Experimental Therapeutics and Immunotherapy Programs, Department of Genitourinary OncologyH. Lee Moffitt Cancer Center and Research InstituteTampaUSA

Personalised recommendations