New approaches to immunotherapy for metastatic castration-resistant prostate cancer.

New approaches to immunotherapy for metastatic castration-resistant prostate cancer. Clin Adv Hematol Oncol. 2019 May;17(5):283-286 Authors: Subudhi SK PMID: 31188806 [PubMed - in process]
Source: Clinical Advances in Hematology and Oncology - Category: Cancer & Oncology Tags: Clin Adv Hematol Oncol Source Type: research

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(University of Texas M. D. Anderson Cancer Center) Prostate cancer that spreads to the bone triggers the destruction of bone tissue that thwarts the effectiveness of immune checkpoint inhibitors. Research points to anti-CTLA-4 and anti-TGF-B combination to protect T cells.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
ConclusionsImmunotherapy with blood-derived DC subsets was feasible and safe and induced functional antigen-specific T cells. The presence of functional antigen-specific T cells correlated with an improved clinical outcome.Trial registrationClinicalTrials.gov identifierNCT02692976, registered 26 February 2016, retrospectively registered.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
AbstractThe most common metastatic lesions of prostate cancer are in bone and can be classified into three distinct pathology subtypes: lytic, blastic, and an indeterminate mixture of both. We investigated a cohort of decalcified formalin-fixed and paraffin-embedded (FFPE) patient specimens from the bone that contained metastatic prostate cancer with lytic or blastic features. These tissue sections were utilized for immunohistochemistry (IHC) staining, isolation of RNA for gene expression, and Digital Spatial Profiling (DSP) of changes in both the tumor and microenvironment. A diverse set of unique immune cell populations ...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Ferumoxytol capped antiprogrammed cell death ‐ligand 1 (PD‐L1) antibodies (aPD‐L1) loaded ultralarge pore mesoporous silica nanoparticles are delivered with image guidance after cabazitaxel (Cbz) chemotherapy for the treatment of prostate cancer. A single session of sequential magnetic resonance image guided chemo‐immunotherapy effecti vely activates T cell infiltration, insisting tumor specific adaptive immunity and tumor rejection superior to systemic aPD‐L1 treatment after Cbz of the same dose. AbstractHerein, ferumoxytol (Fer) capped antiprogrammed cell death ‐ligand 1 (PD‐L1) antibodies (aPD‐L1) loaded...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research
Gold nanospheres can be functionalized with interleukin ‐12 (IL12), a potent anticancer and immunostimulatory cytokine, and a cyclic peptide containing the isoDGR motif (Iso1) that, after coupling to albumin (Iso1‐HSA), recognizes the αvβ3 integrin overexpressed in tumor vessels and on different tumor cell types. Bifunctional nanospheres (Iso1/Au/I L12) increase the infiltration of immune cells and inhibit tumor growth in preclinical tumor models. AbstractThe clinical use of interleukin ‐12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. The hy...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research
Abstract Skeletal metastases are common in genitourinary malignancies-including prostate cancer, renal cell carcinoma, and urothelial cancer-and portend significant morbidity and poor prognosis. The presence of skeletal metastases can result in decreased quality of life and increased morbidity. Strategies can be employed to prevent bone-related complications including lifestyle modifications and dietary supplementation. Additionally, pharmacologic agents exist to prevent bone loss and may be appropriate for patients at high risk of fragility-related or skeletal complications, such as pathologic fracture related to...
Source: Urologic Oncology - Category: Urology & Nephrology Authors: Tags: Urol Oncol Source Type: research
ConclusionsBET Bromodomain inhibition can mediate changes in expression at a genome wide level in prostate cancer cells, resulting in an increased susceptibility to CD8 T cell targeting. These data suggest that combining BET bromodomain inhibition with immune checkpoint blockade may have clinical activity in prostate cancer patients.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Authors: Schepisi G, Brighi N, Cursano MC, Gurioli G, Ravaglia G, Altavilla A, Burgio SL, Testoni S, Menna C, Farolfi A, Casadei C, Tonini G, Santini D, De Giorgi U Abstract Immunotherapy represents the new era of cancer treatment because of its promising results in various cancer types. In urological tumors, the use of the immune-checkpoint inhibitors (ICIs) is increasingly spreading. Although not all patients and not all diseases respond equally well to immunotherapy, there is an increasing need to find predictive markers of response to ICIs. Patient- and tumor-related factors may be involved in primary and secon...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
In this study we review the principles that have guided the engineering of CAR-T cells and the specific prostatic antigens identified as possible targets for immunological and non-immunological therapies. We also provide a state-of-the-art overview of CAR-T cell therapy in PCa, defining the key obstacles to its development and underlining the mechanisms used to overcome these barriers. At present, although there are still many unanswered questions regarding CAR-T cell therapy, there is no doubt that it has the potential to become an important treatment option for urological malignancies.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
ConclusionsThese findings suggest that IDO expression is a mechanism of immune evasion used by prostate cancer and that future clinical trials using T-cell-based immune strategies might best include IDO inhibition.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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