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Prostate-specific membrane antigen-targeted radionuclide therapy as adjunct to Immune checkpoint Inhibition in an immunocompetent murine model for oral squamous cell carcinoma

Michaël Henrotte (UGent) , David Creytens (UGent) , Filip De Vos (UGent) , Benedicte Descamps (UGent) , Lindsey Devisscher (UGent) , Wouter Huvenne (UGent) , Ken Kersemans (UGent) , Sara Neyt (UGent) , Sylvie Rottey (UGent) , Michael Saerens (UGent) , et al.
(2025) 11th European Congress on Head & Neck Oncology, Abstracts.
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Abstract
Introduction Immune checkpoint inhibition (ICI) has a pivotal role in managing advanced oral squamous cell carcinoma (OSCC), but response rates remain low, warranting novel therapeutic interventions. One promising approach is targeting prostate-specific membrane antigen (PSMA). Expressed on neovascular endothelium in OSCC, PSMA may prove a valuable target for targeted radionuclide therapy (TRNT) in these tumours. We investigated the added value of combined TRNT-ICI therapy in a murine model for OSCC. Materials & Methods MOC1 cells (7.5 × 105) were injected into the tongue of male C57BL6/J mice, which were randomised into three treatment groups: 100 MBq [177Lu]Lu-PSMA-I&T (TRNT, n = 5), 5 doses of 200 µg anti-PD-1 (2 doses per week) (ICI, n = 6), or both (TRNT-ICI, n = 6). Treatment response (through tumour volumes) and survival were monitored for up to 90 days. Results Median overall survival was higher in the TRNT-ICI and ICI groups (73 and 75 days, respectively) than in the TRNT group (49 days). Tumour volumes were lower in the TRNT-ICI and ICI groups than in the TRNT group between 7 and 35 days, with a more pronounced tumour suppression in the TRNT-ICI group between 10 and 14 days. Two mice (one from each of the TRNT-ICI and ICI groups) achieved a complete response. Three mice exhibiting ICI-escape phenotypes were excluded. Conclusions This study is the first to explore TRNT as adjunct to ICI in OSCC. Combination therapy demonstrated a brief enhanced tumour suppression compared to ICI alone, warranting further investigations on different treatment regimens for a more durable response.

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MLA
Henrotte, Michaël, et al. “Prostate-Specific Membrane Antigen-Targeted Radionuclide Therapy as Adjunct to Immune Checkpoint Inhibition in an Immunocompetent Murine Model for Oral Squamous Cell Carcinoma.” 11th European Congress on Head & Neck Oncology, Abstracts, European Head & Neck Society, 2025.
APA
Henrotte, M., Creytens, D., De Vos, F., Descamps, B., Devisscher, L., Huvenne, W., … Debacker, J. (2025). Prostate-specific membrane antigen-targeted radionuclide therapy as adjunct to Immune checkpoint Inhibition in an immunocompetent murine model for oral squamous cell carcinoma. 11th European Congress on Head & Neck Oncology, Abstracts. Presented at the 11th European Congress on Head & Neck Oncology (ECHNO 2025), Amsterdam, The Netherlands.
Chicago author-date
Henrotte, Michaël, David Creytens, Filip De Vos, Benedicte Descamps, Lindsey Devisscher, Wouter Huvenne, Ken Kersemans, et al. 2025. “Prostate-Specific Membrane Antigen-Targeted Radionuclide Therapy as Adjunct to Immune Checkpoint Inhibition in an Immunocompetent Murine Model for Oral Squamous Cell Carcinoma.” In 11th European Congress on Head & Neck Oncology, Abstracts. European Head & Neck Society.
Chicago author-date (all authors)
Henrotte, Michaël, David Creytens, Filip De Vos, Benedicte Descamps, Lindsey Devisscher, Wouter Huvenne, Ken Kersemans, Sara Neyt, Sylvie Rottey, Michael Saerens, Christian Vanhove, Tijl Vermassen, and Jens Debacker. 2025. “Prostate-Specific Membrane Antigen-Targeted Radionuclide Therapy as Adjunct to Immune Checkpoint Inhibition in an Immunocompetent Murine Model for Oral Squamous Cell Carcinoma.” In 11th European Congress on Head & Neck Oncology, Abstracts. European Head & Neck Society.
Vancouver
1.
Henrotte M, Creytens D, De Vos F, Descamps B, Devisscher L, Huvenne W, et al. Prostate-specific membrane antigen-targeted radionuclide therapy as adjunct to Immune checkpoint Inhibition in an immunocompetent murine model for oral squamous cell carcinoma. In: 11th European Congress on Head & Neck Oncology, Abstracts. European Head & Neck Society; 2025.
IEEE
[1]
M. Henrotte et al., “Prostate-specific membrane antigen-targeted radionuclide therapy as adjunct to Immune checkpoint Inhibition in an immunocompetent murine model for oral squamous cell carcinoma,” in 11th European Congress on Head & Neck Oncology, Abstracts, Amsterdam, The Netherlands, 2025.
@inproceedings{01JR3JES4M9W23JHNWX39HEH7P,
  abstract     = {{Introduction
Immune checkpoint inhibition (ICI) has a pivotal role in managing advanced oral squamous cell carcinoma (OSCC), but response rates remain low, warranting novel therapeutic interventions. One promising approach is targeting prostate-specific membrane antigen (PSMA). Expressed on neovascular endothelium in OSCC, PSMA may prove a valuable target for targeted radionuclide therapy (TRNT) in these tumours. We investigated the added value of combined TRNT-ICI therapy in a murine model for OSCC.


Materials & Methods
MOC1 cells (7.5 × 105) were injected into the tongue of male C57BL6/J mice, which were randomised into three treatment groups: 100 MBq [177Lu]Lu-PSMA-I&T (TRNT, n = 5), 5 doses of 200 µg anti-PD-1 (2 doses per week) (ICI, n = 6), or both (TRNT-ICI, n = 6). Treatment response (through tumour volumes) and survival were monitored for up to 90 days.


Results
Median overall survival was higher in the TRNT-ICI and ICI groups (73 and 75 days, respectively) than in the TRNT group (49 days). Tumour volumes were lower in the TRNT-ICI and ICI groups than in the TRNT group between 7 and 35 days, with a more pronounced tumour suppression in the TRNT-ICI group between 10 and 14 days. Two mice (one from each of the TRNT-ICI and ICI groups) achieved a complete response. Three mice exhibiting ICI-escape phenotypes were excluded.


Conclusions
This study is the first to explore TRNT as adjunct to ICI in OSCC. Combination therapy demonstrated a brief enhanced tumour suppression compared to ICI alone, warranting further investigations on different treatment regimens for a more durable response.}},
  author       = {{Henrotte, Michaël and Creytens, David and De Vos, Filip and Descamps, Benedicte and Devisscher, Lindsey and Huvenne, Wouter and Kersemans, Ken and Neyt, Sara and Rottey, Sylvie and Saerens, Michael and Vanhove, Christian and Vermassen, Tijl and Debacker, Jens}},
  booktitle    = {{11th European Congress on Head & Neck Oncology, Abstracts}},
  language     = {{eng}},
  location     = {{Amsterdam, The Netherlands}},
  pages        = {{41 slides}},
  publisher    = {{European Head & Neck Society}},
  title        = {{Prostate-specific membrane antigen-targeted radionuclide therapy as adjunct to Immune checkpoint Inhibition in an immunocompetent murine model for oral squamous cell carcinoma}},
  url          = {{https://researchportal.vub.be/en/publications/prostate-specific-membrane-antigen-targeted-radionuclide-therapy--2}},
  year         = {{2025}},
}