The landscape of high-affinity human antibodies against intratumoral antigens

Intratumoral expression of antibody transcripts can be detected across different cancer types and is correlated with positive clinical outcomes. However, the antigens recognized by these antibodies remain largely unknown. Here we inferred the paired sequence of thousands of clonally expanded antibodies using bulk RNA sequencing data from solid tumors in The Cancer Genome Atlas (TCGA). After expressing 283 candidate antibodies in mammalian cells, we individually tested them against a library of twenty thousands full-length human proteins and a library of five thousands membrane-only proteins. Using surface plasmon resonance we confirmed 13 high-affinity antibodies that bind to their targets with KD in the low nanomolar range. Our work provides insights into the antigens that drive B cell responses in human cancers while also directly identifying fully human, high-affinity antibodies against them.