Cancer Vaccines: Emphasis on Pediatric Cancers

Abstract

The success that vaccines have had in the fight with infectious diseases has not been mirrored in their use in the fight against cancer. The major differences are that cancer vaccines have been tested in the therapeutic rather than the prophylactic setting, and in older adults rather than in the pediatric population. Cancers, as well as current standard treatments, are highly immunosuppressive, which further compromises the success of therapeutic vaccines. Cancer is considered to be primarily a disease of the older age and yet many children suffer from or succumb to cancers such as leukemias, glioblastomas, neuroblastomas and sarcomas. Standard therapy, even when curative, is accompanied by serious side effects, including secondary tumors later in life. Due to the greater capacity of a young immune system to recover after cancer treatment, therapeutic vaccines are expected to have a better chance to elicit protective immunity and prevent cancer recurrence in children. In this review, we discuss the current efforts at designing and testing cancer vaccines in children with the focus on specific tumor antigens expressed by pediatric cancers.

Dendritic Cell-Based and Other Vaccination Strategies for Pediatric Cancer

“…Most gliomas can be categorized as either low-grade (LGGs) or high-grade gliomas (HGGs). The latter includes anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) [6,21,22].…”

“…Although it is challenging to assess survival benefit in single-arm studies, several of the clinical trials listed in Table 1 have reported unexpectedly long survival times. For example, De Vleeschouwer et al noted that DC vaccine-treated patients under the age of 35 had an overall survival (OS) of 15.3 months, which was an improvement compared to a Children’s Cancer Group trial which reported that all patients with recurrent malignant glioma died within 1 year [6,46]. In patients with Ewing’s sarcoma, the combination of tumor lysate/KLH-pulsed DC vaccinations with autologous lymphocytes and rhIL-7 administered following standard antineoplastic therapy resulted in higher survival rates and lower recurrence rates compared with patients receiving standard antineoplastic therapy alone [47].…”

“…One of the ten patients treated with the autologous vaccine had complete tumor regression. The superiority of autologous over allogeneic whole tumor cell vaccines is most likely due to the fact that autologous tumor vaccines not only express shared antigens but also unique antigens specific to each individual tumor [6]. In the autologous trial, neuroblasts were transduced with an adenoviral vector encoding IL-2.…”

“…Furthermore, due to long-term toxicity from the intense chemotherapy and radiation regimens, those who do recover are at elevated risk of health consequences later in life, including a higher risk for developing secondary cancers [5]. More targeted therapies are required to overcome these treatment-related side effects and to further improve survival with a favorable long-term quality of life [4,6].…”

“…In the case of immunotherapy, there are specific considerations of safety in the pediatric age group that relate to the immaturity of the immune system. Additionally, the pediatric immune system is more adaptable and vigorous than that of an adult, and immunocompetence can be reconstituted in children even after multiple cytotoxic therapies [6,19]. As a consequence, the response to immunotherapy can differ between children and adults.…”