1. Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response.
- Author
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Goggi, Julian, Khanapur, Shivashankar, Ramasamy, Boominathan, Hartimath, Siddesh, Rong, Tang, Cheng, Peter, Tan, Yun, Yeo, Xin, Jung, Sangyong, Goay, Stephanie, Ong, Seow, Hwang, You, Chandy, K, and Robins, Edward
- Subjects
immune checkpoints ,positron emission tomography (PET) ,potassium channels - Abstract
Immune checkpoint inhibitors have shown great promise, emerging as a new pillar of treatment for cancer; however, only a relatively small proportion of recipients show a durable response to treatment. Strategies that reliably differentiate durably-responding tumours from non-responsive tumours are a critical unmet need. Persistent and durable immunological responses are associated with the generation of memory T cells. Effector memory T cells associated with tumour response to immune therapies are characterized by substantial upregulation of the potassium channel Kv1.3 after repeated antigen stimulation. We have developed a new Kv1.3 targeting radiopharmaceutical, [18F]AlF-NOTA-KCNA3P, and evaluated whether it can reliably differentiate tumours successfully responding to immune checkpoint inhibitor (ICI) therapy targeting PD-1 alone or combined with CLTA4. In a syngeneic colon cancer model, we compared tumour retention of [18F]AlF-NOTA-KCNA3P with changes in the tumour immune microenvironment determined by flow cytometry. Imaging with [18F]AlF-NOTA-KCNA3P reliably differentiated tumours responding to ICI therapy from non-responding tumours and was associated with substantial tumour infiltration of T cells, especially Kv1.3-expressing CD8+ effector memory T cells.
- Published
- 2022