Immunotherapy of Genitourinary Malignancies

Inamoto, Teruo; Azuma, Haruhito

doi:10.1155/2012/397267

Cited by 9 publications

(2 citation statements)

References 60 publications

(64 reference statements)

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“…Low dose cyclophosphamide (shown to decrease the number and function of T reg (25, 26)) was also used alongside GM-CSF to further enhance immune response potential. In addition, RCC is known to be an immune-responsive tumor type (27), whereas immunotherapy for GBM is still in its infancy. Indeed, cancer vaccine immunotherapy strategies for GBM patients require considerable refinement due to the challenges posed by immune resistance and suppression in this tumor type (28).…”

Section: Discussionmentioning

confidence: 99%

A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

Rampling

Peoples

Mulholland

et al. 2016

Clinical Cancer Research

133

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Statement of Translational RelevanceSurvival rates for patients with glioblastoma (GBM) are abysmal, with median overall survival of approximately 15 months. Immunotherapy of GBM is a promising area of investigation, although challenges around identification of novel and immunogenic target antigens exist. IMA950 is a GBM specific vaccine comprising 11 tumor-associated peptides (TUMAPs) developed to address this challenge. We have performed a phase 1 safety and immunogenicity study in newly diagnosed GBM patients using IMA950 plus GM-CSF alongside standard of care chemo-radiotherapy. Our results demonstrate that IMA950 is well tolerated with 90% of patients having a CD8+ T-cell immune response to at least one TUMAP, with 50% responding to two or more TUMAPs. No effect of pre-treatment regulatory T-cell levels on IMA950 immunogenicity was found and steroids did not appear to affect immune responses to the TUMAPs. This data provides evidence to support further development and optimization of IMA950 together with other immunotherapies for GBM. were multi-TUMAP responders, with no important differences between cohorts. No effect of pre-treatment Treg levels on IMA950 immunogenicity was observed and steroids did not affect TUMAP responses. PFS was 74% at 6 months and 31% at 9 months. CONCLUSION: IMA950 plus GM-CSF was well tolerated with the primary immunogenicity endpoint of observing multi-TUMAP responses in at least 30% of patients exceeded.Further development of IMA950 is encouraged.

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Section: Discussionmentioning

confidence: 99%

A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

Rampling

Peoples

Mulholland

et al. 2016

Clinical Cancer Research

133

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“…In addition, these urologic cancers are also known to have the drug-resistant nature against chemotherapeutic drugs [11]. These facts then sturdily encourage and demand exploration of alternative modalities that may improve the outcomes with few side effects [12].…”

Section: Introductionmentioning

confidence: 99%

Possible Chemosensitizing and Potent Anticancer Effects of D-Fraction in Combination with Vitamin C on Three Prevalent Urologic Cancer Cells

Freilich¹,

Moskowitz²,

Feuer³

et al. 2014

JCT

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Chemotherapy is currently one of the most common therapeutic options for cancer patients despite the poor efficacy with considerable side effects. We then examined if D-fraction (DF), a bioactive mushroom extract, could potentiate (poor) anticancer effects of those drugs in vitro. Three urologic cancers, prostate, bladder, and kidney cancers, were tested with various chemotherapeutic drugs and their combinations with DF. Compared to individual drugs alone, combinations of drugs and DF have improved anticancer activity, resulting in the significant (P < 0.05) cell viability reduction in all three cancer cells. As vitamin C (VC) has been postulated to potentiate the bioactivity of DF, this possibility was also examined. The specific combination of DF (300 µg/ml) and VC (200 µM) indeed led to the drastic (≥90%) viability reductions in all three cancer cells. To have a better understanding of such a profound viability reduction, the effect of DF/VC combination on cell cycle was examined next. Cell cycle analysis indicated that this combination induced a G1 cell cycle arrest, which was also confirmed by the down-regulation of specific cell cycle regulators (CDK2, CDK4, and cyclin D 1) detected on western blots. Moreover, it was crucial to address if the DF/VC-induced viability reduction could be also linked to apoptosis. Western blot analysis revealed that anti-apoptotic bcl-2 was down-regulated while pro-apoptotic Bax was up-regulated with DF/VC combination in all cancer cells, indicating induction of apoptosis. Therefore, the DF/VC combination could ultimately induce apoptosis, accounting for the severe cell viability reduction. In conclusion, DF appears to be a promising agent with chemosensitizing effect, enhancing the * Corresponding author. D. Freilich et al. 1403 efficacy of chemotherapeutic drugs, and its combination with VC exhibits a potent anticancer effect, which is far superior to any combinations of drugs and DF tested in three prevalent urologic cancer cells.

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Diet and GU Cancers

Panah

Tanabalan

2014

Urological Oncology

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Immunotherapy of Genitourinary Malignancies

Cited by 9 publications

References 60 publications

A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

A Cancer Research UK First Time in Human Phase I Trial of IMA950 (Novel Multipeptide Therapeutic Vaccine) in Patients with Newly Diagnosed Glioblastoma

Possible Chemosensitizing and Potent Anticancer Effects of D-Fraction in Combination with Vitamin C on Three Prevalent Urologic Cancer Cells

Diet and GU Cancers

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