Novel approaches in cancer immunotherapy

Discov Med. 2016 Apr;21(116):267-74.

Abstract

Our understanding of tumor immunology has exploded in the past 3 decades. The complex relationships between tumor cells, the tumor microenvironment and the immune system cells, especially the cytotoxic and helper T cells and the regulatory T cells are beginning to be elucidated. In this review, we will attempt to provide a brief primer of tumor immunology. Cytokine therapy has historically been the mainstay of immunotherapy in cancers such as melanoma and kidney cancer. We will review some of the advances made with cancer vaccines, with a focus on peptide vaccines, tumor cell vaccines and immune cell vaccines. The pros and cons of nucleic acid-based vaccines including DNA and RNA vaccines will be discussed. Adoptive cell therapy has made significant progress utilizing chimeric antigen-receptor transduced T cells, especially in hematologic malignancies. We will also consider the key targets in checkpoint inhibition, and summarize some of the preclinical and clinical data with respect to checkpoint inhibition. Progress made in the novel immunotherapeutic approach of oncolytic viral therapy will be analyzed. PDL-1 expression by tumor cells and tumor infiltrating lymphocytes has been looked at as a biomarker in clinical trials. Limitations to such an approach and potential candidates for future predictive biomarkers of response to immunotherapy and biomarkers of autoimmunity and adverse reactions will be considered.

MeSH terms

  • Autoimmunity / drug effects
  • Biomarkers, Tumor / immunology
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Costimulatory and Inhibitory T-Cell Receptors / antagonists & inhibitors*
  • Cytokines / adverse effects
  • Cytokines / immunology
  • Cytokines / therapeutic use*
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Molecular Targeted Therapy / methods
  • Neoplasms / therapy*
  • Oncolytic Virotherapy / adverse effects
  • Oncolytic Virotherapy / methods
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Microenvironment / drug effects

Substances

  • Biomarkers, Tumor
  • Cancer Vaccines
  • Costimulatory and Inhibitory T-Cell Receptors
  • Cytokines
  • Immunologic Factors