Frequent and specific immunity to the embryonal stem cell–associated antigen SOX2 in patients with monoclonal gammopathy

Abstract

Specific targets of cellular immunity in human premalignancy are largely unknown. Monoclonal gammopathy of undetermined significance (MGUS) represents a precursor lesion to myeloma (MM). We show that antigenic targets of spontaneous immunity in MGUS differ from MM. MGUS patients frequently mount a humoral and cellular immune response against SOX2, a gene critical for self-renewal in embryonal stem cells. Intranuclear expression of SOX2 marks the clonogenic CD138− compartment in MGUS. SOX2 expression is also detected in a proportion of CD138+ cells in MM patients. However, these patients lack anti-SOX2 immunity. Cellular immunity to SOX2 inhibits the clonogenic growth of MGUS cells in vitro. Detection of anti-SOX2 T cells predicts favorable clinical outcome in patients with asymptomatic plasmaproliferative disorders. Harnessing immunity to antigens expressed by tumor progenitor cells may be critical for prevention and therapy of human cancer.

Small molecule antibody targeting HLA class I inhibits myeloma cancer stem cells by repressing pluripotency-associated transcription factors

“…Spisek et al have reported that Sox2 were highly expressed in CD138 À clonogenic compartment of plasma cells and that anti-Sox2 T cells contribute to prevent disease progression in patients with monoclonal gammopathy. 47 Therefore, our results may support the concept that Sox2 is an attractive target for specific immunotherapy of MM.…”

Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 phenotype

“…Trastuzumab targets the CSC population in gastric tumors J Jiang et al 2006; Spisek et al, 2007;Wang et al, 2009). Several studies have also identified Notch1 and ALDH1 as markers in both normal and malignant stem and progenitor cells (Dontu et al, 2004;Matsui et al, 2004;Ginestier et al, 2007).…”

Vaccination with Human Pluripotent Stem Cells Generates a Broad Spectrum of Immunological and Clinical Responses Against Colon Cancer

“…Most likely, the antigens that were reactive with the H9 immune sera were oncofetal antigens present in both CT26 and the hESCs. Since tumor cells such as myeloma cells do express stem cell-associated antigen Sox2 [47], stem cell immunization might trigger immune response against these gene products that are also expressed by tumor cells. Additionally, the immune response against H9 could lead to antigenic spread to induce protective immunity against CT26 unique tumor antigens, a concept akin to what was proposed to explain the efficiency of xenogeneic antigen immunization [48].…”