Clinical development of immunotherapy for prostate cancer

Noguchi, Masanori; Koga, Noriko; Igawa, Tsukasa; Itoh, Kyogo

doi:10.1111/iju.13397

Cited by 6 publications

(4 citation statements)

References 60 publications

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“…Most of these trials have been conducted at advanced stages of the disease (castration-resistant metastatic PCa), but few at earlier times, for example, at biochemical relapse. [28][29][30][31] Immune Figure 4 The RV001 sequence comprises several promiscuous HLA-class II epitopes and one HLA-B*27:05 restricted epitope. Open access intervention at BCR, when tumor load is limited and immunosuppression absent or limited, might lead to more favorable clinical outcome.…”

Section: Discussionmentioning

confidence: 99%

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

Schuhmacher

Heidu

Balchen³

et al. 2020

J Immunother Cancer

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BackgroundPeptide-based vaccination is a rational option for immunotherapy of prostate cancer. In this first-in-man phase I/II study, we assessed the safety, tolerability and immunological impact of a synthetic long peptide vaccine targeting Ras homolog gene family member C (RhoC) in patients with prostate cancer. RhoC is a small GTPase overexpressed in advanced solid cancers, metastases and cancer stem cells.MethodsTwenty-two patients who had previously undergone radical prostatectomy received subcutaneous injections of 0.1 mg of a single RhoC-derived 20mer peptide emulsified in Montanide ISA-51 every 2 weeks for the first six times, then five times every 4 weeks for a total treatment time of 30 weeks. The drug safety and vaccine-specific immune responses were assessed during treatment and thereafter within a 13-month follow-up period. Serum level of prostate-specific antigen was measured up to 26 months postvaccination.ResultsMost patients (18 of 21 evaluable) developed a strong CD4 T cell response against the vaccine, which lasted at least 10 months following the last vaccination. Three promiscuouslypresented HLA-class II epitopes were identified. Vaccine-specific CD4 T cells were polyfunctional and effector memory T cells that stably expressed PD-1 (CD279) and OX-40 (CD134), but not LAG-3 (CD223). One CD8 T cell response was detected in addition. The vaccine was well tolerated and no treatment-related adverse events of grade ≥3 were observed.ConclusionTargeting of RhoC induced a potent and long-lasting T cell immunity in the majority of the patients. The study demonstrates an excellent safety and tolerability profile. Vaccination against RhoC could potentially delay or prevent tumor recurrence and metastasis formation.Trial registration numberNCT03199872.

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Section: Discussionmentioning

confidence: 99%

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

Schuhmacher

Heidu

Balchen³

et al. 2020

J Immunother Cancer

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“…Prostate cancer (PC) is a most familiar male tumour in Western countries [1]. Although China is a lower incidence area for PC, studies present that the incidence of PC in China is rising linearly in recent years, which fearfully menaces men's health [2].…”

Section: Introductionmentioning

confidence: 99%

Silencing circular RNA circZNF609 restrains growth, migration and invasion by up-regulating microRNA-186-5p in prostate cancer

Jin

Zhao

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Prostate cancer (PC) fearfully impacts men's health. We explored the efficacy and mechanism of circular RNA circZNF609 (circZNF609) on colony formation, viability, apoptosis, migration and invasion and in PC cells. Methods: Colony formation, CCK-8, flow cytometry, migration and invasion assay were respectively used to detect the functions of circZNF609 and microRNA (miR)-186-5p on cell colony ability, viability, apoptosis, migration and invasion. circZNF609 and miR-186-5p expression were changed by cell transfection and tested by RT-qPCR. Moreover, Cleaved-Caspase-3, Cleaved-Caspase-9, matrix metalloproteinase-9 (MMP-9), Vimentin and relate-proteins of cell pathways were examined through Western blot. Results: circZNF609 was highly expressed at PC tissues. circZNF609 declined cell colony ability, viability, migration and invasion and caused apoptosis. Furthermore, circZNF609 negatively regulated miR-186-5p, miR-186-5p inhibitor could reverse impacts of circZNF609. Finally, circZNF609 restrained the YAP1 and AMPK pathways by up-regulating miR-186-5p. Conclusion: Silencing circZNF609 restrained growth, migration and invasion of PC cells by upregulating miR-186-5p via YAP1 and AMPK pathways. HIGHLIGHTS 1. circZNF609 is highly expressed in PC tissues; 2. circZNF609 restrains cell growth, migration and invasion; 3. circZNF609 exerts its function by up-regulating miR-186-5p; 4. circZNF609 exerts its function by YAP1 and AMPK signaling pathways.

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“…Morgenroth et al (2007) [ 4 ] developed the functional chimeric T-cell receptor (CTCR) against prostate stem cell antigens to treat and manage prostate cancer (chimeric alpha-PSCA-beta2/CD3zeta-TCR) [ 4 , 126 ]. Immune checkpoint inhibitors are made to destroy the cancer cells at cell cycle checkpoints, and these revolutionary therapies stimulate T cells to preferentially target prostate cancer cells as a single agent or in combination with other agents [ 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 ]. Immune checkpoint therapies have shown great efficacy in many tumor models, and however CRPC-induced bone metastasis has a sub-optimal response to them [ 138 ], suggesting some immunological niche in the bone environment.…”

Section: Immunotherapymentioning

confidence: 99%

Bone Health Management in the Continuum of Prostate Cancer Disease

Boopathi

Birbe

Shoyele

et al. 2022

Cancers

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Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year survival rate for these patients is 47%. Bone-metastasis-induced early changes in the bone that proceed the osteoblastic response in the bone matrix are monitored and detected via modern magnetic resonance and PET/CT imaging technologies. Various treatment options, such as targeting osteolytic metastasis with bisphosphonates, prednisone, dexamethasone, denosumab, immunotherapy, external beam radiation therapy, radiopharmaceuticals, surgery, and pain medications are employed to treat prostate-cancer-induced bone metastasis and manage bone health. However, these diagnostics and treatment options are not very accurate nor efficient enough to treat bone metastases and manage bone health. In this review, we present the pathogenesis of PCa-induced bone metastasis, its deleterious impacts on vital organs, the impact of metastatic PCa on bone health, treatment interventions for bone metastasis and management of bone- and skeletal-related events, and possible current and future therapeutic options for bone management in the continuum of prostate cancer disease.

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Clinical development of immunotherapy for prostate cancer

Cited by 6 publications

References 60 publications

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

Silencing circular RNA circZNF609 restrains growth, migration and invasion by up-regulating microRNA-186-5p in prostate cancer

Bone Health Management in the Continuum of Prostate Cancer Disease

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