Tumor cell lysates as immunogenic sources for cancer vaccine design

Hum Vaccin Immunother. 2014;10(11):3261-9. doi: 10.4161/21645515.2014.982996.

Abstract

Autologous dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) are a promising immunological tool for cancer therapy. These stimulate the antitumor response and immunological memory generation. Nevertheless, many patients remain refractory to DC approaches. Antigen (Ag) delivery to DCs is relevant to vaccine success, and antigen peptides, tumor-associated proteins, tumor cells, autologous tumor lysates, and tumor-derived mRNA have been tested as Ag sources. Recently, DCs loaded with allogeneic tumor cell lysates were used to induce a potent immunological response. This strategy provides a reproducible pool of almost all potential Ags suitable for patient use, independent of MHC haplotypes or autologous tumor tissue availability. However, optimizing autologous tumor cell lysate preparation is crucial to enhancing efficacy. This review considers the role of cancer cell-derived lysates as a relevant source of antigens and as an activating factor for ex vivo therapeutic DCs capable of responding to neoplastic cells. These promising therapies are associated with the prolonged survival of advanced cancer patients.

Keywords: AM, Cytokine-activated monocytes; Ags, Antigens; CDAMs, Cell death-associated molecules; CRT, Calreticulin; CTLs, Cytotoxic T lymphocytes; DAMPs; DAMPs, Damage-associated molecular patterns; DCs, Dendritic cells; DTH, Delayed-type IV hypersensitivity; GM-CSF, Granulocyte and macrophage colony stimulating factor; HMGB1, High-mobility group box 1 protein; HSPs, Heat shock proteins; ICD, Immunogenic cell death; MAAs, Melanoma-associated antigens; MHC, Major histocompatibility complex; MM, Malignant melanoma; NKT, Natural killer T cell; PAMPs, Pathogen-associated molecular patterns; PBMCs, Peripheral blood mononuclear cells; PCCL, Prostate cancer cell lysate; PD1, Programmed cell death protein 1; PRRs, Pattern recognition receptors; PSA, Prostate specific antigen; RAGE, Receptor for advanced glycation endproducts; SNPs, Single nucleotide polymorphisms; TAAs, Tumor-associated antigens; TAPCells, Tumor antigen presenting cells; TCRs, T cell receptors; TLRs, Toll-like receptors; TNF, Tumor necrosis factor; TRIMEL, Allogeneic melanoma cell lysate; TRIPRO, Allogeneic prostate cell lysate; Toll-like receptors; Tregs, Regulatory T lymphocytes; cancer immunotherapy; dendritic cells; immunogenic cell death.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Cancer Vaccines / immunology*
  • Cell Extracts / immunology
  • Cell Extracts / therapeutic use*
  • Dendritic Cells / immunology*
  • Humans
  • Immunologic Memory / immunology
  • Neoplasms / immunology*
  • Neoplasms / prevention & control
  • Neoplasms / therapy
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Cell Extracts