Related Experiment Video
Updated: Jan 6, 2026
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
CD44v6 expression in non-anaplastic thyroid carcinoma: characterization of candidates for targeted therapy
Adam Stenman1,2, Joachim N Nilsson1,3, Vincenzo Condello4
1Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Background:
CD44v6 is a membranous antigen upregulated in solid tumors and a promising molecular radiotherapy target, especially in anaplastic thyroid carcinoma (ATC). A Phase 1 trial recently launched to evaluate the lutetium-labeled anti-CD44v6 antibody [1⁷⁷Lu]Lu-DOTA-AKIR001 in CD44v6-positive solid tumors. Given limited data in non-ATC, we assessed CD44v6 immunoreactivity in tumors that may progress to a radioiodine-refractory state.
Materials And Methods:
An exploratory cohort of 33 tumors (30 papillary thyroid carcinomas [PTCs], 3 poorly differentiated thyroid carcinomas [PDTCs]) was screened using the VFF-7 antibody, supported by detailed iodine concentration, genetic, and RNA sequencing data. A validation cohort of 40 oncocytic thyroid carcinomas (OTCs), 28 additional PDTCs, and one differentiated high-grade thyroid carcinoma was also screened using two antibody clones, VFF-7 and VFF-18.
Results:
In the exploratory cohort, 10 of 33 tumors (30%) showed focal or diffuse CD44v6 expression, while the rest were negative. Among OTCs in the validation cohort, 15 of 40 (38%) were partially or diffusely positive, and in PDTCs, 14 of 28 (50%) showed focal or diffuse staining. The VFF-7 and VFF-18 clones produced similar patterns.
Conclusions:
Substantial subsets of non-ATCs express CD44v6, indicating that some patients may be candidates for [1⁷⁷Lu]Lu-DOTA-AKIR001 radiotherapy, particularly when conventional treatments are exhausted.
Insights
CD44v6 is expressed in significant subsets of non-anaplastic thyroid carcinomas (non-ATCs). This finding suggests potential eligibility for [1⁷⁷Lu]Lu-DOTA-AKIR001 molecular radiotherapy in these patients.
Area of Science:
- Oncology
- Molecular Imaging
- Radiotherapy
Background:
- CD44v6 is a cell surface glycoprotein overexpressed in various solid tumors.
- It represents a promising target for molecular radiotherapy, particularly in anaplastic thyroid carcinoma (ATC).
- A Phase 1 clinical trial is evaluating [1⁷⁷Lu]Lu-DOTA-AKIR001, an anti-CD44v6 antibody, for treating CD44v6-positive solid tumors.
Purpose of the Study:
- To investigate CD44v6 expression in non-ATC thyroid tumors.
- To assess the potential of CD44v6 as a target for [1⁷⁷Lu]Lu-DOTA-AKIR001 radiotherapy in patients with radioiodine-refractory thyroid cancer.
Main Methods:
- An exploratory cohort of 33 thyroid tumors (papillary and poorly differentiated) was screened for CD44v6 using the VFF-7 antibody.
- A validation cohort of 40 oncocytic thyroid carcinomas and 28 additional poorly differentiated thyroid carcinomas were also screened.
- Immunohistochemistry was performed using two antibody clones (VFF-7 and VFF-18).
Main Results:
- CD44v6 expression was detected in 30% of the exploratory cohort.
- In the validation cohort, 38% of oncocytic thyroid carcinomas and 50% of poorly differentiated thyroid carcinomas showed CD44v6 positivity.
- Both antibody clones yielded comparable staining patterns.
Conclusions:
- Significant proportions of non-anaplastic thyroid carcinomas express CD44v6.
- These findings identify a patient population that may benefit from [1⁷⁷Lu]Lu-DOTA-AKIR001 radiotherapy.
- CD44v6 targeted therapy offers a potential treatment option for patients with advanced or refractory thyroid cancer.
