Skip to main content
SpringerLink
Log in

Reflections on Cancer Vaccines

  • Chapter
  • First Online:
Cancer Immunotherapy Meets Oncology

  • 1856 Accesses

Abstract

Cancer vaccines are likely to soon become mainstream cancer treatment because many of the factors that limit their clinical effectiveness have now been identified. These consist mainly of regulatory circuits in the cancer tissue that limits attack on tissues that are perceived as the body’s own tissue. Since cancer tissues masquerade as self-tissues, they eagerly employ these defense mechanisms such as PD-L1 expression on the tissue and induction of PD-1, TIM3, and Lag3 on the tumor-infiltrating T cells. At the same time cancer tissues are characterized by angiogenesis, in large part mediated by myeloid cells. If self-tissue destruction prevention mediated by PD-L1 expression is blocked by monoclonal antibody either against PD-1 or against PD-L1, and if myeloid suppressor cells are depleted by chemotherapy, the chances for properly adjuvanted cancer vaccines to have substantial clinical impact are excellent. Vaccination carries the promise that the proportion of cancer patients who can benefit from checkpoint blocking will increase substantially.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Belardelli F, Ferrantini M, Proietti E, Kirkwood JM (2002) Interferon-alpha in tumor immunity and immunotherapy. Cytokine Growth Factor Rev 13:119–134

    Article  PubMed  CAS  Google Scholar 

  • Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cheever MA, Schlom J, Weiner LM, Lyerly HK, Disis ML, Greenwood A, Grad O, Nelson WG (2008) Translational research working group developmental pathway for immune response modifiers. Clin Cancer Res 14:5692–5699

    Article  PubMed  CAS  Google Scholar 

  • Feltkamp MC, Smits HL, Vierboom MP, Minnaar RP, de Jongh BM, Drijfhout JW, ter Schegget J, Melief CJ, Kast WM (1993) Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16- transformed cells. Eur J Immunol 23:2242–2249

    Article  PubMed  CAS  Google Scholar 

  • Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12:253–268

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hervas-Stubbs S, Perez-Gracia JL, Rouzaut A, Sanmamed MF, Le Bon A, Melero I (2011) Direct effects of type I interferons on cells of the immune system. Clin Cancer Res 17:2619–2627

    Article  PubMed  CAS  Google Scholar 

  • Heusinkveld M, van der Burg SH (2011) Identification and manipulation of tumor associated macrophages in human cancers. J Transl Med 9:216

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Huber JP, Farrar JD (2011) Regulation of effector and memory T-cell functions by type I interferon. Immunology 132:466–474

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF, Investigators IS (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411–422

    Article  PubMed  CAS  Google Scholar 

  • Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, Drijfhout JW, Wafelman AR, Oostendorp J, Fleuren GJ, Offringa R, van der Burg SH, Melief CJ (2008) Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity. Clin Cancer Res 14:169–177

    Article  PubMed  CAS  Google Scholar 

  • Kenter GG, Welters MJ, Valentijn AR, Lowik MJ, Berends-van der Meer DM, Vloon AP, Essahsah F, Fathers LM, Offringa R, Drijfhout JW, Wafelman AR, Oostendorp J, Fleuren GJ, van der Burg SH, Melief CJ (2009) Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 361:1838–1847

    Article  PubMed  CAS  Google Scholar 

  • Lattanzi L, Rozera C, Marescotti D, D'Agostino G, Santodonato L, Cellini S, Belardelli F, Gavioli R, Ferrantini M (2011) IFN-alpha boosts epitope cross-presentation by dendritic cells via modulation of proteasome activity. Immunobiology 216:537–547

    Article  PubMed  CAS  Google Scholar 

  • Melief CJM, van der Burg SH (2008) Immunotherapy of established (pre-)malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 8:351–360

    Article  PubMed  CAS  Google Scholar 

  • Ngiow SF, Teng MW, Smyth MJ (2011) Prospects for TIM3-targeted anti-tumor immunotherapy. Cancer Res 71:6567–6571

    Article  PubMed  CAS  Google Scholar 

  • Norde WJ, Hobo W, van der Voort R, Dolstra H (2012) Coinhibitory molecules in hematological malignancies: targets for therapeutic intervention. Blood 120:728–736

    Article  PubMed  CAS  Google Scholar 

  • Quakkelaar ED, Melief CJM (2012) Experience with synthetic vaccines for cancer and persistent virus infections in nonhuman primates and patients. Adv Immunol 114:77–106

    Article  PubMed  CAS  Google Scholar 

  • Sabbatini P, Tsuji T, Ferran L, Ritter E, Sedrak C, Tuballes K, Jungbluth AA, Ritter G, Aghajanian C, Bell-McGuinn K, Hensley ML, Konner J, Tew W, Spriggs DR, Hoffman EW, Venhaus R, Pan L, Salazar AM, Diefenbach CM, Old LJ, Gnjatic S (2012) Phase I trial of overlapping long peptides from a tumor self-antigen and poly-ICLC shows rapid induction of integrated immune response in ovarian cancer patients. Clin Cancer Res 18:6497–6508

    Article  PubMed  CAS  Google Scholar 

  • Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, Kendra KL, White RL, Gonzalez R, Kuzel TM, Curti B, Leming PD, Whitman ED, Balkissoon J, Reintgen DS, Kaufman H, Marincola FM, Merino MJ, Rosenberg SA, Choyke P, Vena D, Hwu P (2011) gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med 364:2119–2127

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sikora AG, Jaffarzad N, Hailemichael Y, Gelbard A, Stonier SW, Schluns KS, Frasca L, Lou Y, Liu C, Andersson HA, Hwu P, Overwijk WW (2009) IFN-alpha enhances peptide vaccine-induced CD8+ T cell numbers, effector function, and antitumor activity. J Immunol 182:7398–7407

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Spadaro F, Lapenta C, Donati S, Abalsamo L, Barnaba V, Belardelli F, Santini SM, Ferrantini M (2012) IFN-alpha enhances cross-presentation in human dendritic cells by modulating antigen survival, endocytic routing, and processing. Blood 119:1407–1417

    Article  PubMed  CAS  Google Scholar 

  • Speiser DE, Lienard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, Krieg AM, Cerottini JC, Romero P (2005) Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest 115:739–746

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Tseng CW, Hung CF, Alvarez RD, Trimble C, Huh WK, Kim D, Chuang CM, Lin CT, Tsai YC, He L, Monie A, Wu TC (2008) Pretreatment with cisplatin enhances E7-specific CD8+ T-Cell-mediated antitumor immunity induced by DNA vaccination. Clin Cancer Res 14:3185–3192

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Van der Burg SH, Melief CJM (2011) Therapeutic vaccination against papilloma virus induced malignancies. Curr Opin Immunol 23:252–257

    Article  PubMed  CAS  Google Scholar 

  • Van der Burg SH, Arens R, Melief CJM (2011) Immunotherapy for persistent viral infections and associated disease. Trends Immunol 32:97

    Article  PubMed  CAS  Google Scholar 

  • van Duikeren S, Fransen MF, Redeker A, Wieles B, Platenburg G, Krebber WJ, Ossendorp F, Melief CJ, Arens R (2012) Vaccine-induced effector-memory CD8+ T cell responses predict therapeutic efficacy against tumors. J Immunol 189:3397–3403

    Article  PubMed  CAS  Google Scholar 

  • Welters MJ, Kenter GG, Piersma SJ, Vloon AP, Lowik MJ, Berends-van der Meer DM, Drijfhout JW, Valentijn AR, Wafelman AR, Oostendorp J, Fleuren GJ, Offringa R, Melief CJ, van der Burg SH (2008) Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine. Clin Cancer Res 14:178–187

    Article  PubMed  CAS  Google Scholar 

  • Welters MJ, Kenter GG, de Vos van Steenwijk PJ, Lowik MJ, Berends-van der Meer DM, Essahsah F, Stynenbosch LF, Vloon AP, Ramwadhdoebe TH, Piersma SJ, van der Hulst JM, Valentijn AR, Fathers LM, Drijfhout JW, Franken KL, Oostendorp J, Fleuren GJ, Melief CJ, van der Burg SH (2010) Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses. Proc Natl Acad Sci U S A 107:11895–11899

    Article  PubMed Central  PubMed  Google Scholar 

  • Wolchok JD, Kluger H, Callahan MK, Postow MA, Rizvi NA, Lesokhin AM, Segal NH, Ariyan CE, Gordon RA, Reed K, Burke MM, Caldwell A, Kronenberg SA, Agunwamba BU, Zhang X, Lowy I, Inzunza HD, Feely W, Horak CE, Hong Q, Korman AJ, Wigginton JM, Gupta A, Sznol M (2013) Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 369:122–133

    Article  PubMed  CAS  Google Scholar 

  • Zeestraten EC, Speetjens FM, Welters MJ, Saadatmand S, Stynenbosch LF, Jongen R, Kapiteijn E, Gelderblom H, Nijman HW, Valentijn AR, Oostendorp J, Fathers LM, Drijfhout JW, van de Velde CJ, Kuppen PJ, van der Burg SH, Melief CJ (2013) Addition of interferon-alpha to the p53-SLP(R) vaccine results in increased production of interferon-gamma in vaccinated colorectal cancer patients: a phase I/II clinical trial. Int J Cancer 132:1581–1591

    Article  PubMed  CAS  Google Scholar 

  • Zwaveling S, Ferreira Mota SC, Nouta J, Johnson M, Lipford GB, Offringa R, van der Burg SH, Melief CJ (2002) Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides. J Immunol 169:350–358

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. ISA Pharmaceuticals, J.H. Oortweg 19-21, Leiden, 2333 CH, The Netherlands

    Cornelis J. M. Melief

Authors
  1. Cornelis J. M. Melief
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cornelis J. M. Melief .

Editor information

Editors and Affiliations

  1. Immunotherapy Development Center (IDC), TRON-Translational Oncology University Medical Center, Johannes Gutenberg University, Mainz, Germany

    Cedrik Michael Britten

  2. Department of Immunotherapy Development Center, TRON-Translational Oncology University Medical Center, Johannes Gutenberg-University, Mainz, Germany

    Sebastian Kreiter

  3. Department of Immunotherapy Development Center, TRON-Translational Oncology University Medical Center, Johannes Gutenberg University, Mainz, Germany

    Mustafa Diken

  4. Department of Immunology, University of Tübingen, Tübingen, Germany

    Hans-Georg Rammensee

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Melief, C.J.M. (2014). Reflections on Cancer Vaccines. In: Britten, C., Kreiter, S., Diken, M., Rammensee, HG. (eds) Cancer Immunotherapy Meets Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-05104-8_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-05104-8_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-05103-1

  • Online ISBN: 978-3-319-05104-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation