Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer

Serological analysis of expression cDNA libraries (SEREX) derived from two small cell lung cancer (SCLC) cell lines using pooled sera of SCLC patients led to the isolation of 14 genes, including 4 SOX group B genes (SOX1, SOX 2, SOX3, and SOX21) and ZIC2. SOX group B genes and ZIC2 encode DNA-binding proteins: SOX group B proteins regulate transcription of target genes in t he presence of cofactors, whereas ZIC2 is also suspected to be a transcript ional regulator. These genes are expressed at early developmental stages in the embryonic nervous system, but are down-regulated in the adult. Althoug h SOX2 mRNA can be detected in some adult tissues. ZIC2 is expressed only i n brain and testis, and SOX1, SOX3, and SOX21 transcripts are not detectabl e in normal adult tissues. Of SCLC cell lines tested, 80% expressed ZIC2 mR NA, and SOX1, SOX2, and SOX3 expression was detected in 40%, 50%, and 10%, respectively. SOX group B and ZIC2 antigens elicited serological responses in 30-40% of SCLC patients in this series, at titers up to 1:10(6). In sera from 23 normal adults, no antibody was detected against SOX group B or ZIC 2 proteins except for one individual with low-titer anti-SOX2 antibody. Ser oreactivity against SOX1 and 2 was consistently higher titered than SOX3 an d 21 reactivity, suggesting SOX1 and/or SOX2 as the main antigens eliciting anti-SOX responses. Although paraneoplastic neurological syndromes have be en associated with several SCLC antigens, neurological symptoms have not be en observed in patients with anti-SOX or anti-ZIC2 antibodies.