Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response

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Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response
Title:
Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response
Journal Title:
Cancers
Publication Date:
26 February 2022
Citation:
Goggi, J. L., Khanapur, S., Ramasamy, B., Hartimath, S. V., Rong, T. J., Cheng, P., Tan, Y. X., Yeo, X. Y., Jung, S., Goay, S. S. M., Ong, S. T., Hwang, Y. Y., Chandy, K. G., & Robins, E. G. (2022). Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response. Cancers, 14(5), 1217. https://doi.org/10.3390/cancers14051217
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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the A*STAR - Industry Alignment Fund Prepositioning (IAF-PP) - HBMS
Grant Reference no. : H18/01/a0/018
Description:
ISSN:
2072-6694
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