En masse discovery of anti-cancer human monoclonal antibodies by de novo assembly of immunoglobulin sequences from transcriptomes and genome sequences of cancer tissues

摘要

TO THE EDITOR:Characterization of the tumor-infiltrating B cell immunoglobulin(Ig)repertoire is critical to understanding B cell immunity in tumors and developing monoclonal antibody therapy.However,the generation of specific antibodies for cancer therapy1,2 is a major endeavor,involving a lengthy process of antigen identification,immunization,hybridoma production and,in most cases,antibody humanization.As a radical departure from the conventional approach,we hereby describe a rapid and potentially en masse identification of cancer-specific antibodies directly from human cancer tissues by de novo assembly from transcriptome and genome sequences.Our integrated computational framework was developed and successfully tested for antibody discovery by mining 1945 solid tumor RNA-sequencing-based samples for abundant Ig CDR3 sequences among the TCGA database of glioblastoma multiforme(GBM),lower grade glioma(LGG),lung adenocarcinoma(LUAD),lung squamous carcinoma(LUSC),pancreatic adenocarcinoma(PAAD),and skin cutaneous melanoma(SKCM).