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Immune-Checkpoint Blockade Enhances 225 Ac-PSMA617 Efficacy in a Mouse Model of Prostate Cancer.
- Source :
-
Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2021 Feb; Vol. 62 (2), pp. 228-231. Date of Electronic Publication: 2020 Jul 09. - Publication Year :
- 2021
-
Abstract
- Prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (RNT) may increase tumor immunogenicity. We aimed at exploiting this effect by combining RNT with immunotherapy in a mouse model of prostate cancer (PC). Methods: C57BL/6-mice bearing syngeneic RM1-PGLS tumors were treated with <superscript>225</superscript> Ac-PSMA617, an anti-PD-1 antibody, or both. Therapeutic efficacy was assessed by tumor volume measurements (CT), time to progression (TTP), and survival. Results: PSMA RNT or anti-PD-1 alone tended to prolong TTP (isotype control, 25 d; anti-PD-1, 33.5 d [ P = 0.0153]; RNT, 30 d [ P = 0.1038]) and survival (control, 28 d; anti-PD-1, 37 d [ P = 0.0098]; RNT, 32 d [ P = 0.1018]). Combining PSMA RNT and anti-PD-1 significantly improved disease control compared with either monotherapy. TTP was extended to 47.5 d ( P ≤ 0.0199 vs. monotherapies), and survival to 51.5 d ( P ≤ 0.0251 vs. monotherapies). Conclusion: PSMA RNT and PD-1 blockade synergistically improve therapeutic outcomes in our PC model, supporting the evaluation of RNT and immunotherapy combinations for PC patients.<br /> (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)
- Subjects :
- Actinium
Animals
Cell Line, Tumor
Disease Models, Animal
Humans
Male
Mice
Mice, Inbred C57BL
Programmed Cell Death 1 Receptor immunology
Prostate-Specific Antigen
Prostatic Neoplasms pathology
Dipeptides therapeutic use
Heterocyclic Compounds, 1-Ring therapeutic use
Immune Checkpoint Inhibitors pharmacology
Immunotherapy methods
Prostatic Neoplasms immunology
Prostatic Neoplasms radiotherapy
Subjects
Details
- Language :
- English
- ISSN :
- 1535-5667
- Volume :
- 62
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of nuclear medicine : official publication, Society of Nuclear Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 32646877
- Full Text :
- https://doi.org/10.2967/jnumed.120.246041