Elsevier

Seminars in Oncology

Volume 39, Issue 3, June 2012, Pages 263-275
Seminars in Oncology

Cancer vaccines
Section I: Clinical investigations in a specific cancer type
Vaccines for Melanoma and Renal Cell Carcinoma

https://doi.org/10.1053/j.seminoncol.2012.02.011Get rights and content

The inherent immunogenicity of melanoma and renal cell carcinoma (RCC) has made these tumors a focus of considerable research in vaccine development. Recent data from murine studies of immunosurveillance have highlighted the importance of both innate and adaptive immune responses in shaping a tumor's inherent susceptibility to immune surveillance and immunotherapy. Melanoma has been a useful model for the identification of tumor-associated antigens and a number of putative renal cell antigens have been described more recently. These antigens have been targeted using a variety of vaccine strategies, including protein- and peptide-based vaccines, recombinant antigen-expressing vectors, and whole cell vaccine approaches. While evidence for clinical benefit has been disappointing to date, several current phase III clinical trials are in progress based on promising results from phase II studies. Accumulating data suggest that the tumor microenvironment and mechanisms of immunological escape by established tumors are significant barriers that must be overcome before vaccine therapy can be fully realized. This review will discuss the basis for vaccine development, describe some of the more promising vaccine strategies in development, and mention some of the tumor escape mechanisms that block effective anti-tumor immunity for melanoma and RCC.

Section snippets

Tumor-Associated Antigens for Melanoma and Renal Cell Carcinoma

The basis for immune recognition of tumor cells is the presence of tumor-associated antigens. These antigens are proteins expressed by tumor cells, generally at higher expression levels, at altered points during cell differentiation or in mutated forms. This pattern of expression allows the immune system to detect abnormal cell characteristics, which can be used for targeting a malignant cell for immune-mediated destruction. Table 1 lists selected tumor-associated antigens that have been

Protein- and Peptide-Based Vaccine Approaches

The simplest strategy for vaccine development is to use whole proteins or peptide fragments of defined tumor-associated antigens. Although this approach is straightforward, most protein-/peptide-based vaccines lack significant immunogenicity and have not been able to induce a robust immune response when administered alone. For this reason, most clinical trials of peptide or protein vaccines have used immunologic adjuvants or other agents, such as cytokines or Toll-like receptor agonists,

Recombinant Vector-Based Vaccine Approaches

In contrast to peptide- and protein-based vaccine strategies, recombinant vectors provide a platform for the expression of one or more full-length gene segments. The simplest method is to use a DNA plasmid encoding the gene(s) of interest, although in vivo expression is often difficult to achieve. In contrast, genes can be engineered into viral vectors for vaccination or gene therapy approaches. This offers the advantage of easy manufacturing and delivery to patients and may provide additional

Whole Cell–Based Vaccine Approaches

Another strategy for vaccination is the use of whole cells as vaccines, which are typically irradiated prior to vaccination. Whole cell vaccines can be autologous, in which an individual patient's tumor is resected, irradiated, and prepared for immunization alone or admixes with an immunologic adjuvant. Alternatively, whole cell vaccines can be allogeneic based on a tumor cells or cell lines derived from other patients. Allogeneic whole cell vaccines have the advantage of not requiring

The Tumor Microenvironment and Immunological Escape

Despite the myriad of vaccine strategies that have been attempted in patients with melanoma and RCC, the vast majority of vaccine studies have resulted in disappointing results. This has led some to conclude that vaccination may not be a practical approach for treatment of these diseases.81 The encouraging therapeutic responses observed with nonspecific immunotherapeutic agents, such as IL-2 and ipilimumab, argue for further exploration of vaccines in the management of melanoma and RCC. Recent

Conclusions

The development of vaccine for melanoma and RCC has been a promising approach supported by considerable preclinical investigation and an improved understanding of the molecular and cellular basis of tumor cell recognition and destruction by the immune system. The success of nonspecific agents, such as high-dose IL-2 and anti-CTLA4 monoclonal antibody (ipilimumab), and the identification of tumor-associated antigens in melanoma and RCC tumor cells suggest that vaccination should be useful. A

References (88)

  • D. Jocham et al.

    Adjuvant autologous renal tumour cell vaccine and risk of tumour progression in patients with renal-cell carcinoma after radical nephrectomy: phase III, randomized controlled trial

    Lancet

    (2004)
  • American Cancer Society: Facts and Figures, 2012

  • C. Garbe et al.

    Systematic review of medical treatment in melanoma: current status and future prospects

    Oncologist

    (2011)
  • S. Mocellin et al.

    Interferon-alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis

    J Natl Cancer Inst

    (2010)
  • C.M. Balch et al.

    Final version of 2009 AJCC melanoma staging and classification

    J Clin Oncol

    (2009)
  • G.K. Antony et al.

    Interleukin-2 in cancer therapy

    Curr Med Chem

    (2010)
  • S.F. Hodi et al.

    Improved survival with ipilimumab in patients with metastatic melanoma

    N Engl J Med

    (2011)
  • P.B. Chapman et al.

    Improved survival with vemurafenib in melanoma with BRAF V600E mutation

    N Engl J Med

    (2011)
  • M. Itsumi et al.

    Immunotherapy for renal cell carcinoma

    Clin Dev Immunol

    (2010)
  • Howlader N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975-2008, National Cancer Institute. Bethesda,...
  • M.J. Leveridge et al.

    Recent developments in kidney cancer

    Can Urol Assoc J

    (2011)
  • D.F. McDermott et al.

    Immunotherapy of metastatic renal cell carcinoma

    Cancer J

    (2008)
  • A.M. Molina et al.

    Clinical practice guidelines for the treatment of metastatic renal cell carcinoma: today and tomorrow

    Oncologist

    (2011)
  • D.A. Oble et al.

    Focus on TILs: prognostic significance of tumor infiltrating lymphocytes in human melanoma

    Cancer Immun

    (2009)
  • R. Childs et al.

    Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation

    N Engl J Med

    (2000)
  • Y. Kawakami et al.

    The use of melanosomal proteins in the immunotherapy of melanoma

    J Immunother

    (1998)
  • P.G. Coulie et al.

    A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas

    J Exp Med

    (1994)
  • K.R. Lindsey et al.

    Evaluation of prime/boost regimens using recombinant poxvirus/tyrosinase vaccines for the treatment of patients with metastatic melanoma

    Clin Cancer Res

    (2006)
  • R.F. Wang et al.

    Recognition of an antigenic peptide derived from tyrosinase-related protein-2 by CTL in the context of HLA-A31 and –A33

    J Immunol

    (1998)
  • E. Elkord et al.

    5T4 as a target for immunotherapy in renal cell carcinoma

    Exp Rev Anticancer Ther

    (2009)
  • V. Askoxylakis et al.

    A new peptide ligand for targeting human carbonic anhydrase IX, identified through the phase display technology

    PLoS One

    (2010)
  • N. Peled et al.

    MAGE A3 antigen-specific cancer immunotherapeutic

    Immunotherapy

    (2009)
  • M.J. Scanlan et al.

    Cancer/testis antigens: an expanding family of targets for cancer immunotherapy

    Immunol Rev

    (2002)
  • P.F. Robbins et al.

    A mutated beta catenin gene encodes a melanoma-specific antigen recognized by tumor-infiltrating lymphocytes

    J Exp Med

    (1996)
  • M. Tandon et al.

    Emerging strategies for EPhA2 receptor targeting for cancer therapeutics

    Expert Opin Ther Targets

    (2011)
  • T. Tatsumi et al.

    Disease stage variation in CD4+ and CD8+ T-cell reactivity to the receptor tyrosine kinase EphA2 in patients with renal cell carcinoma

    Cancer Res

    (2003)
  • Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions

    N Engl J Med

    (2007)
  • K. Buscher et al.

    Expression of human endogenous retrovirus K in melanoma and melanoma cell lines

    Cancer Res

    (2005)
  • F. Schiavetti et al.

    A human endogenous retroviral sequence encoding an antigen recognized on melanoma by cytolytic T lymphocytes

    Cancer Res

    (2002)
  • O.J. Finn

    Cancer immunology

    N Engl J Med

    (2008)
  • R.M. Steinman et al.

    Taking dendritic cells into medicine

    Nature

    (2007)
  • A.B. Frey et al.

    Signaling defects in anti-tumor T cells

    Immunol Rev

    (2008)
  • R. Kennedy et al.

    Multiple roles for CD4+ T cells in anti-tumor immune responses

    Immunol Rev

    (2008)
  • E. Elkord et al.

    T regulatory cells in cancer: recent advances and therapeutic potential

    Expert Opin Biol Ther

    (2010)
  • Cited by (22)

    • Amplifying antitumor T cell immunity with versatile drug delivery systems for personalized cancer immunotherapy

      2022, Medicine in Drug Discovery
      Citation Excerpt :

      To facilitate the delivery of these antigens and promote the vaccination efficacy of autologous tumor sources, various drug delivery systems including nanoparticles and hydrogels have been designed to deliver ATVs locally or systemically for generating protective immunity, breaking immune resistance and inducing durable tumor-specific immunity [53,58-64]. The absence of co-stimulatory molecules and presence of immunosuppressive signals in tumor microenvironment have significantly weakened the immunization effect of ATVs [65]. To overcome these issues for extending the clinical application of ATVs, David J. Mooney and co-workers fabricated a whole tumor cell vaccine platform that co-loads liver tumor cells and adjuvants in a cryogel structure for inducing a potent and long-lasting immune response against tumor cells [64].

    • Systemically administered gp100 encoding DNA vaccine for melanoma using water-in-oil-in-water multiple emulsion delivery systems

      2013, International Journal of Pharmaceutics
      Citation Excerpt :

      To elicit potent immune response a DNA vaccine must be delivered and transported across cell membrane of the antigen presenting cells (APCs) in sufficient concentration while protected from nuclease mediated destruction (Allison and Byars, 1991). Polar and anionic nature of a plasmid DNA molecule does not readily allow transfer across the biological membranes (Kaufman, 2012). Therefore, one of the major challenges in DNA vaccination is optimal gene delivery to target immune cells.

    • Three-dimensional cryogels for biomedical applications

      2019, Journal of Biomedical Materials Research - Part A
    View all citing articles on Scopus

    Conflict of interest: none.

    View full text