Immunoprevention of cancer through targeting of precancerous stem cells

Abstract

Recently we have identified a new type of cancer cells called precancerous stem cells (pCSCs) and proposed that cancer may arise from a lengthy developing process of tumor initiating cells (TICs) → pCSCs → cancer stem cells (CSCs) → cancer cells, which is in parallel to histological changes of hyperplasia (TICs) → precancer (pCSCs) → carcinoma (CSCs/cancer cells). Since the progression of pCSCs to cancer was suppressed in immunocompetent mice (IC) mice, we hypothesized that pCSCs can be used as a tumor vaccine. Here we report that the mice injected with pCSCs developed anti‐tumor immunity, because they were resistant to the challenge of tumor cell lines with different origin. The anti‐tumor immunity could be transferred into severe immunodeficient disease (SCID) mice, which appeared to be mediated by pCSC protein‐specific T cells. This finding suggests that cancer can be prevented by immunoprevention through targeting of pCSCs or precancerous lesions. The novel concept was further supported by immunoprevention with KaovaccineTM, a biological response modifier (BRM), from the spontaneous development of lung cancer in the SP‐C/p53‐273H mice transgenic with mutated human p53 (p53‐273H) under the transcriptional control of the lung‐specific human surfactant protein C (SP‐C) promoter. Taken together, our studies indicate that immunoprevention of cancer is feasible through targeting of pCSCs.