A team led by Ludwig Lausanne’s Alexandre Harari and Director George Coukos devised a highly efficient method to generate large numbers of immune cells specifically engineered to recognize neoantigens—small fragments of randomly mutated proteins unique to a patient’s cancer—and destroy the tumors that express them. The method, named NeoScreen and described in Nature Biotechnology in November, could significantly improve the generation of engineered T cells for personalized cancer immunotherapies. Alexandre, George and their colleagues computationally analyzed the genomes of tumor cells and identified potential neoantigens. They then engineered B cells to be antigen presenting cells, pulsed them with the potential neoantigens so that they’d present the peptides and grew them in co-cultures with tumor infiltrating T lymphocytes (TILs). This approach resulted in the selective and dramatic expansion of the most useful T cells—the ones specifically equipped to target tumor cells—against melanoma and lung, ovarian and colon cancers. The T cell receptors on these cells could be cloned and inserted into other T cells to generate large numbers of tumor-targeting cells. T cells produced using NeoScreen recognized genuine neoantigens in tumors and could be used for adoptive cell therapy to induce tumor regressions in mouse models.
This article appeared in the February 2022 issue of Ludwig Link. Click here to download a PDF (1 MB).