RT Journal Article
SR Electronic
T1 The landscape of high-affinity human antibodies against intratumoral antigens
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.06.430058
DO 10.1101/2021.02.06.430058
A1 Goran Rakocevic
A1 Irina Glotova
A1 Ines de Santiago
A1 Berke Cagkan Toptas
A1 Milena Popovic
A1 Milos Popovic
A1 Dario Leone
A1 Andrew L. Stachyra
A1 Raphael Rozenfeld
A1 Deniz Kural
A1 Daniele Biasci
YR 2021
UL http://biorxiv.org/content/early/2021/05/03/2021.02.06.430058.abstract
AB High expression of immunoglobulin transcripts is often detected in human tumours and correlates with favourable clinical outcomes across different cancer types. However, the antigens recognized by such immunoglobulins (Ig) and their biological significance remain largely unknown. We computationally inferred the paired sequence of thousands of clonally expanded Ig using bulk RNA sequencing data from solid tumors in The Cancer Genome Atlas (TCGA). After expressing 283 Ig as recombinant antibodies in mammalian cells, we individually tested them against a library of twenty thousands full-length human proteins and an additional library of six thousand structurally intact membrane proteins, thus identifying their candidate target antigens. Using surface plasmon resonance we then confirmed 16 high-affinity antibodies that bind to their targets with KD in the nanomolar range. Our work provides insights into the antigens that drive B cell responses in human cancers, while also obtaining fully human, high-affinity recombinant antibodies against them.Competing Interest StatementGR, IG, BCT, Milena P, Milos P, ALS, RR, DB and DK are participants in Totient's Equity Incentive Plan. GR, IDS, BCT and DB are coinventors on patents assigned to Totient, Inc.