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Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy—a preclinical study using a syngeneic breast cancer model
- Source :
- European Journal of Nuclear Medicine and Molecular Imaging, European Journal of Nuclear Medicine and Molecular Imaging, 48 (4)
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- PurposeIt was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [177Lu]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy.MethodsIn vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [177Lu]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [177Lu]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 × 200 μg; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment.Results[177Lu]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [177Lu]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [177Lu]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls.ConclusionApplication of [177Lu]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates.
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
[177Lu]Lu-DOTA-folate
Lutetium
NF9006 breast tumor cells
Mice
03 medical and health sciences
Folic Acid
0302 clinical medicine
Immune system
In vivo
Cell Line, Tumor
Neoplasms
Animals
Medicine
Radiology, Nuclear Medicine and imaging
Adverse effect
Radioisotopes
Folate receptor
biology
business.industry
General Medicine
Immunotherapy
3. Good health
Radiation therapy
030104 developmental biology
CTLA-4
030220 oncology & carcinogenesis
biology.protein
Cancer research
Original Article
[Lu-177]Lu-DOTA-folate
Radiopharmaceuticals
Antibody
business
Subjects
Details
- ISSN :
- 16197089 and 16197070
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- European Journal of Nuclear Medicine and Molecular Imaging
- Accession number :
- edsair.doi.dedup.....370a114cb55f3f4591c01edffcaf5301