Antigen-Specific T-Cell Response from Dendritic Cell Vaccination Using Cancer Stem-Like Cell-Associated Antigens

Abstract

Glioblastoma multiforme is the most aggressive primary brain tumor, with current treatment remaining palliative. Immunotherapies harness the body’s own immune system to target cancers and could overcome the limitations of conventional treatments. One active immunotherapy strategy uses dendritic cell (DC)-based vaccination to initiate T cell-mediated anti-tumor immunity. It has been proposed that cancer stem-like cells (CSCs) may play a key role in cancer initiation, progression and resistance to current treatments. However, whether using human CSC antigens may improve the anti-tumor effect of DC vaccination against human cancer is unclear. In this study, we explored the suitability of CSCs as sources of antigens for DC vaccination again human GBM, with the aim of achieving CSC-targeting and enhanced anti-tumor immunity. We found that CSCs express high levels of tumor associated antigens (TAAs) as well as major histocompatibility complex (MHC) molecules. Furthermore, DC vaccination using CSC antigens elicited antigen-specific T cell responses against CSCs. DC vaccination induced interferon (IFN) -γ production is positively correlated with the number of antigen-specific T cells generated. Finally, using a 9L CSC brain tumor model, we demonstrate that vaccination with DCs loaded with 9L CSCs, but not daughter cells or conventionally cultured 9L cells, induced CTLs against CSCs, and prolonged survival in animals bearing 9L CSC tumors. Understanding how immunization with CSCs generates superior anti-tumor immunity may accelerate development of CSC-specific immunotherapies and cancer vaccines.

Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells

“…[37][38][39][40] However, the mechanisms involved have yet to be fully defined and no experimental evidence has been provided for direct targeting of CSCs by CSC-DC vaccine-induced anti-CSC immunity. We report herein that the therapeutic efficacy of our CSC-DC vaccine was associated with significantly inhibited metastasis to the lung.…”

“…So far, studies in these regards, while limited, have focused on cellular immunity, e.g., higher production of interferon g (IFNg) by T cells, 40 or enhanced tumor infiltration of CD8…”

Concise Review: Transmissible Animal Tumors as Models of the Cancer Stem-Cell Process

“…This may be of particular relevance for DFTD, where vaccination strategies have been proposed as a method of halting the devastating spread and extinction threat [2,9], while similar approaches are being evaluated for CTVT [45]. Although investigational, data suggest that for some tumors the CSC component represents a particular target for vaccine-based therapy [46][47][48]; as such, identification of a putative CSC for these tumors may be helpful.…”

Stem cell technology and engineering for cancer treatment

“…Cancer antigens could be loaded onto DCs by nano-sized carriers including nanoparticles or nanoemulsions (Park et al, 2013). Studies on mice have shown DCs primed by CSCs antigens effectively induced immune response to tumor cells and prolonged survival (Lu et al, 2015;Ning et al, 2012;Xu et al, 2009). Treatment with DCs loaded with CSCs-derived antigen induced a tumorspecific immune response stronger than that induced by DCs loaded with normal tumor cells (Dillman et al, 2012;Jachetti et al, 2013).…”