Long-term first-in-man Phase I/II study of an adjuvant dendritic cell vaccine in patients with high-risk prostate cancer after radical prostatectomy.
Biomarkers
/ blood
Cancer Vaccines
/ administration & dosage
Dendritic Cells
/ immunology
Humans
Male
Middle Aged
Neoplasm Metastasis
/ prevention & control
Outcome Assessment, Health Care
/ methods
Prostate
/ immunology
Prostate-Specific Antigen
/ blood
Prostatectomy
/ adverse effects
Prostatic Neoplasms
/ blood
Secondary Prevention
/ methods
Survival Analysis
Time
Vaccines, Synthetic
/ administration & dosage
dendritic cells
prostate cancer
radical prostatectomy
vaccine
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
12
07
2021
accepted:
02
11
2021
pubmed:
12
11
2021
medline:
22
2
2022
entrez:
11
11
2021
Statut:
ppublish
Résumé
Patients with high-risk prostate cancer (PC) can experience biochemical relapse (BCR), despite surgery, and develop noncurative disease. The present study aimed to reduce the risk of BCR with a personalized dendritic cell (DC) vaccine, given as adjuvant therapy, after robot-assisted laparoscopic prostatectomy (RALP). Twelve weeks after RALP, 20 patients with high-risk PC and undetectable PSA received DC vaccinations for 3 years or until BCR. The primary endpoint was the time to BCR. The immune response was assessed 7 weeks after surgery (baseline) and at one-time point during the vaccination period. Among 20 patients, 11 were BCR-free over a median of 96 months (range: 84-99). The median time from the end of vaccinations to the last follow-up was 57 months (range: 45-60). Nine patients developed BCR, either during (n = 4) or after (n = 5) the vaccination period. Among five patients diagnosed with intraductal carcinoma, three experienced early BCR during the vaccination period. All patients that developed BCR remained in stable disease within a median of 99 months (range: 74-99). The baseline immune response was significantly associated with the immune response during the vaccination period (p = 0.015). For patients diagnosed with extraprostatic extension (EPE), time to BCR was longer in vaccine responders than in non-responders (p = 0.09). Among 12 patients with the International Society of Urological Pathology (ISUP) grade 5 PC, five achieved remission after 84 months, and all mounted immune responses. Patients diagnosed with EPE and ISUP grade 5 PC were at particularly high risk of developing postsurgical BCR. In this subgroup, the vaccine response was related to a reduced BCR incidence. The vaccine was safe, without side effects. This adjuvant first-in-man Phase I/II DC vaccine study showed promising results. DC vaccines after curative surgery should be investigated further in a larger cohort of patients with high-risk PC.
Sections du résumé
BACKGROUND
Patients with high-risk prostate cancer (PC) can experience biochemical relapse (BCR), despite surgery, and develop noncurative disease. The present study aimed to reduce the risk of BCR with a personalized dendritic cell (DC) vaccine, given as adjuvant therapy, after robot-assisted laparoscopic prostatectomy (RALP).
METHODS
Twelve weeks after RALP, 20 patients with high-risk PC and undetectable PSA received DC vaccinations for 3 years or until BCR. The primary endpoint was the time to BCR. The immune response was assessed 7 weeks after surgery (baseline) and at one-time point during the vaccination period.
RESULTS
Among 20 patients, 11 were BCR-free over a median of 96 months (range: 84-99). The median time from the end of vaccinations to the last follow-up was 57 months (range: 45-60). Nine patients developed BCR, either during (n = 4) or after (n = 5) the vaccination period. Among five patients diagnosed with intraductal carcinoma, three experienced early BCR during the vaccination period. All patients that developed BCR remained in stable disease within a median of 99 months (range: 74-99). The baseline immune response was significantly associated with the immune response during the vaccination period (p = 0.015). For patients diagnosed with extraprostatic extension (EPE), time to BCR was longer in vaccine responders than in non-responders (p = 0.09). Among 12 patients with the International Society of Urological Pathology (ISUP) grade 5 PC, five achieved remission after 84 months, and all mounted immune responses.
CONCLUSION
Patients diagnosed with EPE and ISUP grade 5 PC were at particularly high risk of developing postsurgical BCR. In this subgroup, the vaccine response was related to a reduced BCR incidence. The vaccine was safe, without side effects. This adjuvant first-in-man Phase I/II DC vaccine study showed promising results. DC vaccines after curative surgery should be investigated further in a larger cohort of patients with high-risk PC.
Substances chimiques
Biomarkers
0
Cancer Vaccines
0
UV1 vaccine
0
Vaccines, Synthetic
0
Prostate-Specific Antigen
EC 3.4.21.77
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
245-253Informations de copyright
© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.
Références
Pierorazio PM, Walsh PC, Partin AW, Epstein JI. Prognostic Gleason grade grouping: data based on the modified Gleason scoring system. BJU Int. 2013;111(5):753-760.
Artibani W, Porcaro AB, De Marco V, Cerruto MA, Siracusano S. Management of biochemical recurrence after primary curative treatment for prostate cancer: a review. Urol Int. 2018;100(3):251-262.
Nguyen PL, Alibhai SM, Basaria S, et al. Adverse effects of androgen deprivation therapy and strategies to mitigate them. Eur Urol. 2015;67(5):825-836.
Kasper S. Stem cells: the root of prostate cancer? J Cell Physiol. 2008;216(2):332-336.
Boettcher AN, Usman A, Morgans A, VanderWeele DJ, Sosman J, Wu JD. Past, current, and future of immunotherapies for prostate cancer. Front Oncol. 2019;9:7-12.
Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411-422.
Gulley JL, Borre M, Vogelzang NJ, et al. Phase III trial of PROSTVAC in asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. J Clin Oncol. 2019;37(13):1051-1061.
Lilleby W, Gaudernack G, Brunsvig PF, et al. Phase I/IIa clinical trial of a novel hTERT peptide vaccine in men with metastatic hormone-naive prostate cancer. Cancer Immunol Immunother. 2017;66(7):891-901.
Tryggestad AMA, Bigalke I, Lilleby W, et al. Immunogenic properties and antitumor effects of novel therapeutic dendritic cell vaccines expressing hTERT and Survivin antigens in metastatic prostate cancer patients. J Cancer Sci Clin Ther. 2020;4(3):388-402.
Axcrona K, Vlatkovic L, Hovland J, Brennhovd B, Kongsgaard U, Giercksky KE. Robot-assisted laparoscopic prostatectomy in a 68-year-old patient with previous heart transplantation and pelvic irradiation. J Robot Surg. 2011;6(1):81-83.
Briganti A, Blute ML, Eastham JH, et al. Pelvic lymph node dissection in prostate cancer. Eur Urol. 2009;55(6):1251-1265.
Bennett VS, Varma M, Bailey DM. Guidelines for the macroscopic processing of radical prostatectomy and pelvic lymphadenectomy specimens. J Clin Pathol. 2007;61(6):713-721.
Epstein JI, Allsbrook WC, Amin MB, Egevad LL, ISUP Grading Committee. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol. 2005;29:1228-1242.
Lilleby W, Stensvold A, Mills IG, Nesland JM. Disseminated tumor cells and their prognostic significance in nonmetastatic prostate cancer patients. Int J Cancer. 2013;133(1):149-155.
Wang P, Gao Q, Suo Z, et al. Identification and characterization of cells with cancer stem cell properties in human primary lung cancer cell lines. PLoS One. 2013;8(3):e57020.
Saebøe-Larssen S, Fossberg E, Gaudernack G. mRNA-based electrotransfection of human dendritic cells and induction of cytotoxic T lymphocyte responses against the telomerase catalytic subunit (hTERT). J Immunol Methods. 2002;259(1-2):191-203.
Jarnjak-Jankovic S, Hammerstad H, Saebøe-Larssen S, Kvalheim G, Gaudernack G. A full scale comparative study of methods for generation of functional dendritic cells for use as cancer vaccines. BMC Cancer. 2007;7(1):575-579.
Subklewe M, Geiger C, Lichtenegger FS, et al. New generation dendritic cell vaccine for immunotherapy of acute myeloid leukemia. Cancer Immunol Immunother. 2014;63(10):1093-1103.
Zobywalski A, Javorovic M, Frankenberger B, et al. Generation of clinical grade dendritic cells with capacity to produce biologically active IL-12p70. J Transl Med. 2007;5(1):18.
Burnell SEA, Spencer-Harty S, Howarth S, et al. Utilisation of the STEAP protein family in a diagnostic setting may provide a more comprehensive prognosis of prostate cancer. PLoS One. 2019;14(8):e0220456.
Wright GL, Haley C, Beckett ML, Schellhammer PF. Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1(1):18-28.
Floisand Y, Bigalke I, Josefsen D, et al. A WT-1 and PRAME “Fast-DC” immunotherapy as a potential post-remission strategy for AML. Blood. 2020;136(Suppl 1):11.
Ihlaseh-Catalano SM, Drigo SA, De Jesus CM, et al. STEAP1 protein overexpression is an independent marker for biochemical recurrence in prostate carcinoma. Histopathology. 2013;63(5):678-685.
Rosellini M, Santoni M, Mollica V, et al. Treating prostate cancer by antibody-drug conjugates. Int J Mol Sci. 2021;22(4):1551.
Wargowski E, Johnson LE, Eickhoff JC, et al. Prime-boost vaccination targeting prostatic acid phosphatase (PAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) using Sipuleucel-T and a DNA vaccine. J Immunother Cancer. 2018;6(1):21.
Xu H, Wang F, Li H, et al. Prostatic acid phosphatase (PAP) predicts prostate cancer progress in a population-based study: the renewal of PAP? Dis Markers. 2019;2019:7090545.
Ross A, Armstrong AJ, Pieczonka CM, et al. A comparison of sipuleucel-T (sip-T) product parameters from two phase III studies: PROVENT in active surveillance prostate cancer and IMPACT in metastatic castrate-resistant prostate cancer (mCRPC). J Clinical Oncol. 2020;38(6 Suppl):321.
Kishan AU, Cook RR, Ciezki JP, et al. Radical prostatectomy, external beam radiotherapy, or external beam radiotherapy with brachytherapy boost and disease progression and mortality in patients with Gleason score 9-10 prostate cancer. JAMA. 2018;319(9):896-905.
Fridman WHW, Pagès FF, Sautès-Fridman CC, Galon JJ. The immune contexture in human tumors: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298-306.
Laheurte C, Dosset M, Vernerey D, et al. Distinct prognostic value of circulating anti-telomerase CD4+ Th1 immunity and exhausted PD-1+/TIM-3+ T cells in lung cancer. Br J Cancer. 2019;121(5):405-416.
Luo C, Chen J, Chen L. Exploration of gene expression profiles and immune microenvironment between high and low tumor mutation burden groups in prostate cancer. Int Immunopharmacol. 2020;86:106709.
Lawrence MG, Porter LH, Clouston D, et al. Knowing what's growing: Why ductal and intraductal prostate cancer matter. Sci Transl Med. 2020;12(533):eaaz0152.
Kimura K, Tsuzuki T, Kato M, et al. Prognostic value of intraductal carcinoma of the prostate in radical prostatectomy specimens. Prostate. 2014;74(6):680-687.
Faisal FA, Tosoian JJ, Han M, Macura KJ, Pavlovich CP, Lotan TL. Clinical, pathological and oncologic findings of radical prostatectomy with extraprostatic extension diagnosed on preoperative prostate biopsy. J Urol. 2019;201(5):937-942.
Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO classification of tumors of the urinary system and male genital organs-Part B: Prostate and bladder tumors. Eur Urol. 2016;70(1):106-119.
Epstein JI, Zelefsky MJ, Sjoberg DD, et al. A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol. 2016;69(3):428-435.