Joint funding from the Cambridge Enterprise Technology Investment Fund and Cancer Research Horizons has been awarded to researchers Marc de la Roche (Department of Biochemistry) and Maike de la Roche (Cancer Research UK Cambridge Institute).
This funding will allow them to continue their development of Superkiller CAR-T cells, a novel strategy for supercharging potency of cytotoxic immune cells towards cancer cells expressing the LGR5 protein, advancing it to clinical study. The therapy is highly effective against malignant cells from two of the most common causes of cancer-related deaths – colorectal cancer and liver cancer.
Dr Marc de la Roche said, ‘I am delighted with the progress on this translational project. Advanced CRC and HCC are highly intractable malignancies and funding from the TIF and CRH will provide an excellent vehicle for taking our Superkiller CAR-T cell therapy to clinical trials, ultimately impacting human health.’
The TIF/CRH funding builds on a recent publication from the de la Roche laboratories. The paper ‘Novel immunotherapeutics against LGR5 to target multiple cancer types’ published in EMBO Molecular Medicine, outlines the urgent clinical and therapeutic need for developing precision immunotherapies targeting colorectal and liver cancer, and B cell malignancies. LGR5 is highly expressed in cells from these cancers and serves as an excellent beacon for recruitment of killer immune cells or toxic compounds. The dearth of validated antibodies to LGR5 has hindered the development of corresponding immunotherapies. The highly specific antibody to LGR5 developed in this study has provided the foundation for creating new immunotherapeutic strategies targeting cancer.
The paper develops develops the LGR5 antibody as ADC-, BiTE- and CAR-based therapeutic modalities and in vivo studies established efficacy in targeting a murine model of human pre-B-ALL tumours.
This study establishes a versatile α-LGR5 antibody and a portfolio of effective immunotherapeutics targeting LGR5-expressing malignancies.