Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis. This study evaluated the safety, immune responses, and clinical outcomes of Wilms' tumor 1 (WT1) peptide-loaded dendritic cell (DC) vaccination combined with hormone or chemotherapeutic agents in mCRPC patients.

Methods

WT1 peptide-loaded mature DCs were administered intradermally and the adjuvant OK-432 every 2–4 weeks. WT1-specific immune responses were assayed using ELISpot, HLA-tetramer, and CD107a assays.

Results

Vaccination was well tolerated with no severe adverse events. WT1-specific immune responses were significantly enhanced in patients with stable disease (SD), along with reduced regulatory T cells. A PSA reduction of >50% was achieved in 35.7% of patients. Median overall survival (mOS) was 28.5 months, exceeding the Halabi nomogram's estimate (19.0 months). Patients with WT1-specific immune responses exhibited significantly longer mOS, suggesting a link between WT1-specific immunity and favorable outcomes.

Conclusion

This immunotherapy approach shows promise for improving survival in mCRPC patients.

CONFLICT OF INTEREST STATEMENT

The authors declare no competing interests.

Open Research

DATA AVAILABILITY STATEMENT

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

REFERENCES

1Bray F, Laversanne M, Sung H, Ferly J, Siegel RL, Soerjomataram I, et al. Global cancer statistic 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74(3): 229–263. https://doi.org/10.3322/caac.21834
10.3322/caac.21834
PubMed Web of Science® Google Scholar
2 Seer Cancer Statics. http://seer.cancer.gov/statfacts/html/prost.html
Google Scholar
3Anguille S, Smits EL, Lion E, Tendeloo VF, Berneman ZN. Clinical use of dendritic cells for cancer therapy. Lancet Oncol. 2014; 15(7): e257–e267.
10.1016/S1470-2045(13)70585-0
CAS PubMed Web of Science® Google Scholar
4Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. Dendritic ells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020; 20(1): 7–24.
10.1038/s41577-019-0210-z
CAS PubMed Web of Science® Google Scholar
5Podrazil M, Horvath R, Becht E, Rozkova D, Bilkova P, Sochorova K, et al. Phase I/II clinical trial of dendritic-cell based immunotherapy (DCVAC/PCa) combined with chemotherapy in patients with metastatic, castration-resistant prostate cancer. Oncotarget. 2015; 6(20):18192205.
10.18632/oncotarget.4145
Web of Science® Google Scholar
6Vogelzang NJ, Beer TM, Gerritsen W, Oudard S, Wiechno P, Kukielka-Budny B, et al. Efficacy and safety of autologous dendritic cell-based immunotherapy, docetaxel, and prednisone vs placebo in patients with metastatic castration-resistant prostate cancer: the VIABLE phase 3 randomized clinical trial. JAMA Oncol. 2022; 8(4): 546–552.
10.1001/jamaoncol.2021.7298
PubMed Web of Science® Google Scholar
7Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010; 363(5): 411–422.
10.1056/NEJMoa1001294
CAS PubMed Web of Science® Google Scholar
8Sugiyama H. WT1 (Wilms' tumor gene 1): biology and cancer immunotherapy. Jpn J Clin Oncol. 2010; 40(5): 377–387.
10.1093/jjco/hyp194
PubMed Web of Science® Google Scholar
9Greg JL, Brown KE, Mintz EM, Piontkivska H, Fraizer GC. Analysis of gene expression in prostate cancer epithelial and interstitial stromal cells using laser capture microdissection. BMC Cancer. 2010; 10: 165.
10.1186/1471-2407-10-165
PubMed Google Scholar
10Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009; 15(17): 5323–5337.
10.1158/1078-0432.CCR-09-0737
PubMed Web of Science® Google Scholar
11Ogasawara M. Wilms' tumor 1-targeting cancer vaccine: recent advancement and future perspectives. Hum Vaccin Immunother. 2024; 20(1):2296735.
10.1080/21645515.2023.2296735
PubMed Google Scholar
12Tano T, Okamoto M, Kan S, Bando T, Goda H, Nakashiro K, et al. Immunochemoradiotherapy for patients with oral squamous cell carcinoma: augmentation of OK-432-induced helper T cell 1 response by 5FU and X-ray irradiation. Neoplasia. 2013; 15(7): 805–814.
10.1593/neo.13488
CAS PubMed Web of Science® Google Scholar
13Okamoto M, Furuichi S, Nishioka Y, Oshikawa T, Tano T, Ahmed SU, et al. Expression of toll-like receptor 4 on dendritic cells is significant for anti-cancer effect of dendritic cell-based immunotherapy in combination with an active component of OK-432, a streptococcal preparation. Cancer Res. 2004; 64(15): 5461–5470.
10.1158/0008-5472.CAN-03-4005
CAS PubMed Web of Science® Google Scholar
14Ogasawara M, Miyashita M, Ota S. Vaccination of urological cancer patients with WT1 peptide-pulsed dendritic cells in combination with molecular targeted therapy or conventional chemotherapy induces immunological and clinical responses. Ther Apher Dial. 2018; 22(3): 266–277.
10.1111/1744-9987.12694
CAS PubMed Web of Science® Google Scholar
15Scher HI, Halabi S, Tannock I, Morris M, Stemberg CN, Carducci MA, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the prostate cancer clinical trials working group. J Clin Oncol. 2008; 26(7): 1148–1159. https://doi.org/10.1200/JCO.2007.12.4487
10.1200/JCO.2007.12.4487
PubMed Web of Science® Google Scholar
16Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3): 205–216.
10.1093/jnci/92.3.205
CAS PubMed Web of Science® Google Scholar
17Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013; 48(3): 452–458.
10.1038/bmt.2012.244
CAS PubMed Web of Science® Google Scholar
18Halabi S, Lin C-Y, Kelly KK, Fizazi KS, Moul JW, Kaplan EB, et al. Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2014; 32(7): 671–677. https://doi.org/10.1200/JCO.2013.52.3696
10.1200/JCO.2013.52.3696
PubMed Web of Science® Google Scholar
19Kongsted P, Borch TH, Ellebaek E, Iversen TZ, Andersen R, Met O, et al. Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration-resstant prostate cancer: a randomized phase II study. Cytotherapy. 2017; 19(4): 500–513. https://doi.org/10.1016/j.jcyt.2017.01.007
10.1016/j.jcyt.2017.01.007
CAS PubMed Web of Science® Google Scholar
20Xi H-B, Wang G-X, Fu B, Liu W-P, Li Y. Survivin and PSMA loaded dendritic cell vaccine for the treatment of prostate cancer. Biol Pharm Bull. 2015; 38(6): 827–835.
10.1248/bpb.b14-00518
CAS PubMed Web of Science® Google Scholar
21Vergati M, Cereda V, Madan RA, Gulley JL, Huen N-Y, Rogers CJ, et al. Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre-versus post-vaccination. Cancer Immunol Immunother. 2011; 60(2): 197–206. https://doi.org/10.1007/s00262-010-0927-9
10.1007/s00262-010-0927-9
PubMed Web of Science® Google Scholar
22Mo L, Chen Q, Zhang X, Shi X, Wei L, Zheng D, et al. Depletion of regulatory T cells by anti-ICOS antibody enhances anti-tumor immunity of tumor cell vaccine in prostate cancer. Vaccine. 2017; 35(43): 5932–5938.
10.1016/j.vaccine.2017.08.093
CAS PubMed Web of Science® Google Scholar
23Hirayama M, Nishikawa H, Nagata Y, Tsuji T, Kato T, Kageyama S, et al. Overcoming regulatory T-cell suppression by a lyophilized preparation of Streptococcus pyogenes. Eur J Immunol. 2013; 43(4): 989–1000.
10.1002/eji.201242800
CAS PubMed Web of Science® Google Scholar
24Sartor O, de Bono JS. Metastatic prostate cancer. N Engl J Med. 2018; 378(7): 645–657.
10.1056/NEJMra1701695
CAS PubMed Web of Science® Google Scholar
25Freedland SJ, Davis M, Epstein AJ, Arondekar B, Ivanova JI. Real-world treatment patterns and overall survival among men with metastatic castration-resistant prostate cancer (mCRPC) in the US Medicare population. Prostate Cancer Prostatic Dis. 2024; 27(2): 327–333.
10.1038/s41391-023-00725-8
CAS PubMed Web of Science® Google Scholar
26Penson DF, Armstrong AJ, Concepcion R, Agarwal N, Olsson C, Karsh L, et al. Enzalutamide versus bicalutamide in castration-resistant prostate cancer: The STRIVE trial. J Clin Oncol. 2016; 34(18): 2098–2106.
10.1200/JCO.2015.64.9285
CAS PubMed Web of Science® Google Scholar
27Ogasawara M, Miyashita M, Yamagishi Y, Ota S. Dendritic cell vaccination combined with a conventional chemotherapy for patients with relapsed or advanced pancreatic ductal adenocarcinoma: a single-center phase I/II trial. Ther Apher Dial. 2021; 25: 415–424.
10.1111/1744-9987.13659
CAS PubMed Web of Science® Google Scholar

Volume29, Issue4

45th Annual Meeting of Japanese Society for Apheresis

August 2025

Pages 568-576

Combined immunotherapy employing Wilms' tumor 1 peptide-pulsed dendritic cells and hormone or chemotherapeutic agents in patients with metastatic castration resistant prostate cancer

Abstract

Introduction

Methods

Results

Conclusion

CONFLICT OF INTEREST STATEMENT

Open Research

DATA AVAILABILITY STATEMENT

REFERENCES

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Combined immunotherapy employing Wilms' tumor 1 peptide-pulsed dendritic cells and hormone or chemotherapeutic agents in patients with metastatic castration resistant prostate cancer

Abstract

Introduction

Methods

Results

Conclusion

CONFLICT OF INTEREST STATEMENT

Open Research

DATA AVAILABILITY STATEMENT

REFERENCES

References

Related

Information