Dendritic Cell-Based and Other Vaccination Strategies for Pediatric Cancer

Abstract

Dendritic cell-based and other vaccination strategies that use the patient's own immune system for the treatment of cancer are gaining momentum. Most studies of therapeutic cancer vaccination have been performed in adults. However, since cancer is one of the leading causes of death among children past infancy in the Western world, the hope is that this form of active specific immunotherapy can play an important role in the pediatric population as well. Since children have more vigorous and adaptable immune systems than adults, therapeutic cancer vaccines are expected to have a better chance of creating protective immunity and preventing cancer recurrence in pediatric patients. Moreover, in contrast to conventional cancer treatments such as chemotherapy, therapeutic cancer vaccines are designed to specifically target tumor cells and not healthy cells or tissues. This reduces the likelihood of side effects, which is an important asset in this vulnerable patient population. In this review, we present an overview of the different therapeutic cancer vaccines that have been studied in the pediatric population, with a main focus on dendritic cell-based strategies. In addition, new approaches that are currently being investigated in clinical trials are discussed to provide guidance for further improvement and optimization of pediatric cancer vaccines.

Keywords: dendritic cells; immunotherapy; pediatric cancer; tumor vaccination.

Figure 1

Mechanistic principles of anti-cancer vaccination. The most important types of tumor vaccines are dendritic cell (DC), tumor cell (TC), and peptide vaccines. The common mechanism of action for all tumor vaccines is the induction of tumor antigen-specific cytotoxic T-lymphocytes (CTLs). These CTLs are capable of recognizing and killing TCs that express tumor antigen fragments, designated peptides, on their cell surface in the context of major histocompatibility complex (MHC) molecules. The recognition of the peptide/MHC is conferred by the T-cell receptor (TCR). (A) DCs are professional antigen-presenting cells (APCs) and are thus highly equipped to induce tumor antigen-specific CTLs. DCs, either from autologous or allogeneic origin, can be loaded with antigenic material through different ways (e.g., by pulsing with peptides, or with TC lysates). These tumor-antigen loaded DCs are usually administered in combination with immune adjuvants for improved immune stimulation. (B) Autologous or allogeneic TCs, inactivated (inact.) by lysis, can also be used in combination with immune adjuvants to induce tumor antigen-specific CTLs, which are in turn capable of killing TCs that express the corresponding tumor antigenic peptide(s). (C) Peptides, administered together with immune adjuvants, are also being used for therapeutic cancer vaccination purposes. Peptide vaccine-based approaches rely on the presence of functionally competent APCs in vivo for effective stimulation of a CTL immune response.