Recent Developments in Cell-based Immune Therapy for Neuroblastoma

Abstract

Neuroblastoma (NB) is a common and aggressive tumor of early childhood. To date, treatment with chemotherapy, surgery, and radiation therapy has resulted in suboptimal outcomes in those with advanced disease. Immune-based treatments hold promise for patients with recurrent or advanced NB. Here, recent preclinical studies and early stage (phase I) clinical trials using cellular therapeutic approaches for NB are reviewed, including studies of natural killer cells, gammadelta T cells, chimeric receptor expressing T cells, dendritic cells, and allogeneic hematopoietic cell transplant.

Doxorubicin treatment induces tumor cell death followed by immunomodulation in a murine neuroblastoma model

“…These innate cellular phagocytes are considered to have a pivotal role in the mechanism of tumor immunity (2,14–17). In particular, BM-derived immature DCs phagocytose, mature and later contribute to immune reactions against cancer cells (2,13,18,19). Alternatively, tumor-associated macrophages infiltrate the tumor, engulfing dead cells and inducing a tolerogenic reaction to tumor cells (15,16,20).…”

“…However, a passive, antibody-based immunotherapeutic approach increased the two-year event-free survival rate, indicating that immunological mechanisms are capable of promoting the eradication of high-risk neuroblastoma cells (10,12). Investigation into the potential immunological benefits of chemotherapeutic agents may improve conventional chemotherapeutic regimens and help to establish novel immunological therapies for high-risk neuroblastoma (13). …”

NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors

“…30 To date, treatment with chemotherapy, surgery and radiation therapy has resulted in suboptimal outcomes in patients with advanced disease. 33 Surgery is not effective on the disseminated neuroblastoma and neither are radiation and chemotherapy, which additionally cause severe toxic side effects on healthy tissues. The bad prognosis in the advanced stage of neuroblastoma is the reason to create new therapeutic alternatives more effective, selective and with less side effects than the currently available therapies.…”

Cellular Immunotherapy for Neuroblastoma: A Review of Current Vaccine and Adoptive T Cell Therapeutics

“…In patients with neuroblastoma, development of a safe and effective vaccine for generalized use may be further hampered by the heterogeneity of tumor pathobiology, since some malignancies undergo spontaneous regression, while others are highly metastatic and minimally responsive to most intensive therapies. Moreover, downregulation of major histocompatibility complex (MHC) and co-stimulatory molecules by neuroblastoma cells may limit the effectiveness of any tumor-specific T cell immune response induced by the vaccine [17–20]. …”

“…Gonzalez et al described the generation of CE7R CAR-expressing CD8 + clones targeting CD171 [38], the L1 adhesion molecule that is overexpressed by neuroblastoma cells [17, 39, 40]. The CAR-T cells were used in a Phase I trial for patients with recurrent/refractory disease, and of the 6 patients treated, no severe toxicities were observed and one had a partial, but un-sustained, response after CE7R T cell infusion [41].…”