Discovering therapeutic antibodies designed by nature

Nature Medicine publication

Nature Medicine publication

December 22, 2014

Published in Nature Medicine: on-line 22 December 2014

High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma

A team of researchers from the Netherlands Cancer Institute, AIMM Therapeutics, Leiden University Medical Center and the Welcome Trust Sanger Institute led by AIMM’s SAB member Ton Schumacher has identified neoantigens arising from melanoma-specific mutations that are recognized by intratumoral CD4+ T cells. This exciting discovery has implications for our understanding of tumor targeting by the immune system and may lead to novel strategies to treat melanoma patients.

To identify the neo antigens the researchers made use of B cells immortalized by AIMSelect technology, which are highly potent antigen presenting cells (APC). Melanoma cells were subjected to exome sequencing to identify melanoma specific mutations. Peptides encompassing these mutations were subsequently tested for their ability to stimulate the patient’s CD4+ T cells using the patients own immortalized B cells as APC. Because AIMM’s immortalized B cells do not stimulate CD4+ T cells in the absence of antigens, peptides containing neo-antigens could be easily identified. The study highlights the huge advantage of AIMM’s immortalized B cells as APC above Dendritic cells which cannot be expanded in vitro or EBV-transformed B cells which strongly activate T cells in the absence of neo antigens.