Using HLA LOH as a Biomarker in Targeting Cancers: Julian Molina, MD, PhD

“HLA LOH is the tool that is going to allow us to discriminate normal cells from cancer cells. It's going to allow the target construct to be able to be more specific and to prevent some of those off-target effects. We're starting with HLA A2 because this is the most prevalent allele. The key issue is going to be for us to identify this group of patients that have HLA loss in the tumors because those are the candidates for future studies.”

Julian Molina, MD, PhD, professor, oncology, Mayo Clinic, and colleagues are conducting the BASECAMP-1 to identify patients with relapsed solid tumors with human leukocyte antigen (HLA) loss of heterozygosity (LOH) as a future target for mesothelin (MSLN) and carcinoembryonic antigen (CEA)-targeted Tmod chimeric antigen receptor (CAR) T-cell therapies. Molina presented the study at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021.

A2 Biotherapeutics is developing the Tmod CAR T-cell therapies, preclinical data on which were also presented at SITC 2021. These data demonstrated the technology’s robust protective effect on surrogate normal human cells in vitro, even in mixed-cell populations, while also yielding a robust cytotoxic effect on tumor cells in xenograft models.

GeneTherapyLive spoke with Molina to learn more about the role of HLA LOH as a useful biomarker in cancer cells. He also discussed the Tempus genomic sequencing technology being used in the study.

REFERENCES

1. A2 Bio to Highlight Program Updates in Two Presentations at SITC 2021. News release. A2 Bio Therapeutics. November 1, 2021. https://www.businesswire.com/news/home/20211101005077/en/A2-Bio-to-Highlight-Program-Updates-in-Two-Presentations-at-SITC-2021
2. Molina J, Go W, Kopetz S, et al. BASECAMP-1: an observational study to identify relapsed solid tumor patients with human leukocyte antigen (HLA) loss of heterozygosity (LOH) and leukapheresis for future CAR T-cell therapy. Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington, DC. Abstract 491.