Article

Cancer immunotherapy: moving beyond current vaccines.

Surgery Branch of the Center for Cancer Research at the National Cancer Institute, Building 10, Room 2B42, 10 Center Drive, MSC 1502 Bethesda, Maryland 20892-1502, USA.
Nature Medicine (Impact Factor: 28.05). 10/2004; 10(9):909-15. DOI: 10.1038/nm1100
Source: PubMed

ABSTRACT Great progress has been made in the field of tumor immunology in the past decade, but optimism about the clinical application of currently available cancer vaccine approaches is based more on surrogate endpoints than on clinical tumor regression. In our cancer vaccine trials of 440 patients, the objective response rate was low (2.6%), and comparable to the results obtained by others. We consider here results in cancer vaccine trials and highlight alternate strategies that mediate cancer regression in preclinical and clinical models.

Download full-text

Full-text

Available from: Nicholas P Restifo, Jun 30, 2015
1 Follower
 · 
281 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin 10 is a cytokine with the ability to reduce or terminate inflammation. Chronic viral infection, such as infection of chronic hepatitis B, hepatitis C and HIV, has increased levels of interleukin 10 in peripheral blood. Serum IL-10 levels are also high in certain cancers. Blocking IL-10 signalling at the time of immunisation clears chronic viral infection and prevents tumour growth in animal models. We review recent advances in this area, with the emphasis on potential use of this novel strategy to treat chronic viral infection and cancer in human. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cellular Immunology 01/2015; 293(2):126-129. DOI:10.1016/j.cellimm.2014.12.012 · 1.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tumor antigenic peptides therapeutics is a promising field for cancer immunotherapy; advantages include convenient synthesis and modification of antigenic peptides, as well as little toxicity associated with its administration. Vaccination of the peptides derived from tumor-associated antigen (TAA) was specifically designed for T cells in the context of MHC molecules. In the past decades, tumor antigenic peptides have been examined in clinic but numbered success has been obtained because of the stability of peptide and delivery approaches, consequently leading to an inefficient antigen presentation and low response rates in cancer patients. Thus, the appropriate and efficient peptide vaccine carrier systems still continue to be a major obstacle. However, both sipuleucel-T vaccine and anti-CTLA-4 antibody have been approved by FDA for the treatment of metastatic prostate cancer and melanoma, respectively. PLGA has been recently used as the adjuvant to elicit enhanced immune responses while delivering tumor antigenic peptides. Intracellular delivery of the peptides derived from TAA into DCs would prolong antigen presentation of APC to T cells. This article aims to describe a new delivery method regarding tumor antigenic peptides and rationales of DCs-based vaccination.
    Current Medicinal Chemistry 05/2014; 21(21). DOI:10.2174/092986732121140521100224 · 3.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer vaccines can induce robust activation of tumor-specific CD8+ T cells that can destroy tumors. Understanding the mechanism by which cancer vaccines work is essential in designing next-generation vaccines with more potent therapeutic activity. We recently reported that short peptides emulsified in poorly biodegradable, Incomplete Freund's Adjuvant (IFA) primed CD8+ T cells that did not localize to the tumor site but accumulated at the persisting, antigen-rich vaccination site. The vaccination site eventually became a T cell graveyard where T cells responded to chronically released gp100 peptide by releasing cytokines, including interferon - γ (IFN-γ), which in turn upregulated Fas ligand (FasL) on host cells, causing apoptosis of Fas(+) T cells. T cells that escaped apoptosis rapidly became exhausted, memory formation was poor, and therapeutic impact was minimal. Replacing the non-biodegradable IFA-based formulation with water-based, short-lived formulation in the presence of immunostimulatory molecules allowed T cells to traffic to tumors, causing their regression. In this review, we discuss recent advances in immunotherapeutic approaches that could enhance vaccine-primed immune cells fitness and render the tumor microenvironment more accessible for immune cell infiltration.
    The international journal of biochemistry & cell biology 05/2014; 53. DOI:10.1016/j.biocel.2014.04.019 · 4.24 Impact Factor