Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette–Guerin for patients with non-muscle invasive bladder cancer

Obara, Wataru; Hara, Isao; Kato, Yoichiro; Kato, Renpei; Inoue, Keiji; Sato, Fuminori; Mimata, Hiromitsu; Nakamura, Yusuke; Fujioka, Tomoaki

doi:10.1007/s00262-018-2197-x

Cited by 14 publications

(25 citation statements)

References 29 publications

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“…DEPDC1 is highly expressed in various kinds of cancers, like bladder cancer, hepatocellular carcinoma, lung cancer, and nasopharyngeal carcinoma (18, 24–27). Its abnormal expression drives the progression of carcinogenesis and the malignant behavior of cancer cells (12, 28).…”

Section: Discussionmentioning

confidence: 99%

“…Currently, DEPDC1 promoting cancer development was gradually discovered and had been widely considered as a putative oncogene. The role of DEPDC1 in cancers was mainly found in bladder cancer (8, 10, 24, 29, 30). It was reported that DEPDC1 was significantly increased in bladder carcinoma and necessary for the proliferation of cancer cells (8).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer

Zhao

Sui

et al. 2019

Front. Oncol.

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DEP domain containing 1 (DEPDC1) is a novel tumor-associated gene, which is aberrantly expressed in multiple types of cancer and involves in tumorigenesis and cancer progression. Here, we examined the functional involvement and underlying mechanism of DEPDC1 in breast cancer. In this study, the immunohistochemistry results demonstrated that DEPDC1 was high-expressed in breast cancer tissues compared with the paired adjacent normal breast tissues, and its tendency at protein level was consistent with mRNA level from TCGA data. Moreover, DEPDC1 mRNA level revealed the strongest association with poor prognosis and development in breast cancer. In vitro assays showed that DEPDC1 overexpression resulted in significant promotion of proliferation by regulating cell cycle in MCF-7 cells, whilst an opposite effect was found in the MDA-MB-231 cells with DEPDC1 deletion. Notably, further investigation indicated DEPDC1's ability of promoting breast cancer cells migration and invasion. In addition, we discovered that DEPDC1 caused hyper-activation of PI3K/AKT/mTOR signaling in breast cancer cells. Therefore, the increased DEPDC1 expression in breast cancer is correlated with disease progression and poor survival, which suggested that DEPDC1 might be a potential therapeutic target against this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer

Zhao

Sui

et al. 2019

Front. Oncol.

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“…In view of our results, further investigation is warranted to elucidate the complete immune response (other immune subsets of cells or local and systemic immune biomarkers) induced by M. brumae compared to BCG to completely understand the role of mycobacteria in modulating the tumor microenvironment. Different strategies for superficial bladder treatment are currently being proposed: diverse bacteria 30 – 32 , modified virus 33 , 34 , chemotherapeutic agents 35 , molecules that target specific immune receptors 36 , peptide vaccines 37 , plant derived compounds 38 , etc. Mycobacteria can have a role to synergy to these treatments, as has been already demonstrated 35 , 37 , 38 , enabling to reduce the toxicity and resistance to a single treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Different strategies for superficial bladder treatment are currently being proposed: diverse bacteria 30 – 32 , modified virus 33 , 34 , chemotherapeutic agents 35 , molecules that target specific immune receptors 36 , peptide vaccines 37 , plant derived compounds 38 , etc. Mycobacteria can have a role to synergy to these treatments, as has been already demonstrated 35 , 37 , 38 , enabling to reduce the toxicity and resistance to a single treatment. Further understanding of the immune reaction associated with mycobacteria treatment could be critical for identifying the benefits of new immunotherapeutic possibilities.…”

Section: Discussionmentioning

confidence: 99%

Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice

Noguera-Ortega

Rabanal

Gómez-Mora

et al. 2018

Sci Rep

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The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as Mycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses of ex vivo splenocytes cultured with mycobacteria antigens. In both BCG- and M. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used.

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“…For example, in a preclinical study, researchers observed that, in a syngeneic mouse model of oral cancer comprised of mouse tonsil-derived epithelial cells stably expressing HPV-16 E6 and E7 genes along with H-ras oncogene (mEER), intranasal HPV E6/E7 peptide vaccination or single checkpoint antibodies failed to elicit responses in most mice; however, 4-1BB agonist antibody along with either CD40 agonist antibody or CTLA-4 blockade eliminated the majority of established mEER tumors, and even produced a curative efficacy and a high safety profile against orally implanted mEER tumors [40]. For another example, in a phase II clinical trial, researchers performed immunotherapy with two peptide cancer vaccines in combination with intravesical bacillus Calmette-Guerin (BCG) for patients with non-muscle invasive bladder cancer (NMIBC) and demonstrated that this combinatory immunotherapy had good immunogenicity and safety and resulted in a 2 year RFS rate 74.0% in all patients, suggesting the cancer vaccines with a combinatory mode may provide benefit to patients for preventing recurrence of NMIBC [41].…”

Section: Np Entrapping Various Ags For Delivering Cancer Vaccinesmentioning

confidence: 99%

Vaccines Developed for Cancer Immunotherapy

Shen¹,

Qu²,

Liu³

et al. 2018

Immunization - Vaccine Adjuvant Delivery System and Strategies

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Vaccines have been successfully used for prophylaxis of infectious diseases for a long time and in the last decades have inspired researchers to make products with similar immunological mechanisms for cancer immunotherapy, which has been developed rapidly into clinical applications and has shown remarkable therapeutic efficacy, as exemplified by chimeric Ag receptor T cell (CAR-T cell) and immune checkpoint inhibitor-based therapies which can efficiently strengthen the body's immune system to fight against cancer, but they are also expensive. Therefore, encouraged by recent success of cancer immunotherapy, scientists are actively developing the low-cost tumor Ag-based vaccines, which, however, usually exhibit weak immunostimulating effects and, therefore, are often formulated with nanoparticulate carriers to form a vaccine adjuvant-delivery system (VADS), which can not only enhance the efficacy but also mitigate the off-target toxicity associated with conventional anticancer vaccines. These nanoparticulate carrierbased VADSs have demonstrated multiple functions, such as targetedly triggering Ag-presenting cells, reeducating tumor-associated macrophages (TAM) to function as tumor suppressor agent, and eliciting robust cytotoxic T lymphocytes (CTLs) to kill tumor cells. This chapter introduces multifunctional VADS that have been engineered with nanoparticulate carriers, including polymeric-, lipid-, metallic-, and cell-based nanoparticles, and used as an alternative to the existent tools for cancer immunotherapy.

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Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette–Guerin for patients with non-muscle invasive bladder cancer

Abstract: Cancer peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.

Cited by 14 publications

References 29 publications

High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer

High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer

Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice

Vaccines Developed for Cancer Immunotherapy

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