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

Julian L. Goggi; Shivashankar Khanapur; Boominathan Ramasamy; Siddesh V. Hartimath; Tang Jun Rong; Peter Cheng; Yun Xuan Tan; Xin Yi Yeo; Sangyong Jung; Stephanie Shee Min Goay; Seow Theng Ong; You Yi Hwang; K. George Chandy; Edward G. Robins

doi:10.3390/cancers14051217

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

Julian L. Goggi, Shivashankar Khanapur, Boominathan Ramasamy, Siddesh V. Hartimath, Tang Jun Rong, Peter Cheng, Yun Xuan Tan, Xin Yi Yeo, Sangyong Jung, Stephanie Shee Min Goay, Seow Theng Ong, You Yi Hwang, K. George Chandy, Edward G. Robins

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

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, [¹⁸ F]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 [¹⁸ F]AlF-NOTA-KCNA3P with changes in the tumour immune microenvironment determined by flow cytometry. Imaging with [¹⁸ F]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.

Original language	English
Article number	1217
Journal	Cancers
Volume	14
Issue number	5
DOIs	https://doi.org/10.3390/cancers14051217
Publication status	Published or Issued - 1 Mar 2022
Externally published	Yes

Keywords

Immune checkpoints
Positron emission tomography (PET)
Potassium channels

ASJC Scopus subject areas

Oncology
Cancer Research

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10.3390/cancers14051217

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@article{77526a57fa784d42b125c13494b38834,

title = "Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response",

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, [18 F]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 [18 F]AlF-NOTA-KCNA3P with changes in the tumour immune microenvironment determined by flow cytometry. Imaging with [18 F]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.",

keywords = "Immune checkpoints, Positron emission tomography (PET), Potassium channels",

author = "Goggi, {Julian L.} and Shivashankar Khanapur and Boominathan Ramasamy and Hartimath, {Siddesh V.} and Rong, {Tang Jun} and Peter Cheng and Tan, {Yun Xuan} and Yeo, {Xin Yi} and Sangyong Jung and Goay, {Stephanie Shee Min} and Ong, {Seow Theng} and Hwang, {You Yi} and Chandy, {K. George} and Robins, {Edward G.}",

note = "Funding Information: Funding: This work was supported by the Institute of Bioengineering and Bioimaging (IBB) and in part by Singapore{\textquoteright}s Health and Biomedical Sciences (HBMS) Industry Alignment Fund PrePositioning (IAF-PP) grant H18/01/a0/018, administered by the Agency for Science, Technology and Research (A*STAR). The content is solely the responsibility of the authors and does not necessarily represent the official views of A*STAR. Funding Information: This work was supported by the Institute of Bioengineering and Bioimaging (IBB) and in part by Singapore?s Health and Biomedical Sciences (HBMS) Industry Alignment Fund PrePositioning (IAF-PP) grant H18/01/a0/018, administered by the Agency for Science, Technology and Research (A*STAR). The content is solely the responsibility of the authors and does not necessarily represent the official views of A*STAR. Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = mar,

day = "1",

doi = "10.3390/cancers14051217",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

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T1 - Imaging Kv1.3 Expressing Memory T Cells as a Marker of Immunotherapy Response

AU - Goggi, Julian L.

AU - Khanapur, Shivashankar

AU - Ramasamy, Boominathan

AU - Hartimath, Siddesh V.

AU - Rong, Tang Jun

AU - Cheng, Peter

AU - Tan, Yun Xuan

AU - Yeo, Xin Yi

AU - Jung, Sangyong

AU - Goay, Stephanie Shee Min

AU - Ong, Seow Theng

AU - Hwang, You Yi

AU - Chandy, K. George

AU - Robins, Edward G.

N1 - Funding Information: Funding: This work was supported by the Institute of Bioengineering and Bioimaging (IBB) and in part by Singapore’s Health and Biomedical Sciences (HBMS) Industry Alignment Fund PrePositioning (IAF-PP) grant H18/01/a0/018, administered by the Agency for Science, Technology and Research (A*STAR). The content is solely the responsibility of the authors and does not necessarily represent the official views of A*STAR. Funding Information: This work was supported by the Institute of Bioengineering and Bioimaging (IBB) and in part by Singapore?s Health and Biomedical Sciences (HBMS) Industry Alignment Fund PrePositioning (IAF-PP) grant H18/01/a0/018, administered by the Agency for Science, Technology and Research (A*STAR). The content is solely the responsibility of the authors and does not necessarily represent the official views of A*STAR. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/3/1

Y1 - 2022/3/1

N2 - 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, [18 F]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 [18 F]AlF-NOTA-KCNA3P with changes in the tumour immune microenvironment determined by flow cytometry. Imaging with [18 F]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.

AB - 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, [18 F]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 [18 F]AlF-NOTA-KCNA3P with changes in the tumour immune microenvironment determined by flow cytometry. Imaging with [18 F]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.

KW - Immune checkpoints

KW - Positron emission tomography (PET)

KW - Potassium channels

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U2 - 10.3390/cancers14051217

DO - 10.3390/cancers14051217

M3 - Article

AN - SCOPUS:85125199424

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 5

M1 - 1217

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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