Increased indoleamine 2,3-dioxygenase activity and expression in prostate cancer following targeted immunotherapy

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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AbstractA novel cancer vaccine consisting of 20 mixed peptides (KRM-20) was designed to induce cytotoxic T lymphocytes (CTL) against twelve different tumor-associated antigens. The aim of this phase II trial was to examine whether KRM-20 in combination with docetaxel and dexamethasone enhances the antitumor effects in patients with castration-resistant prostate cancer (CRPC). In this double-blind, placebo-controlled, randomized phase II study, we enrolled chemotherapy-na ïve patients with CRPC from ten medical centers in Japan. Eligible patients were randomly assigned 1:1 centrally to receive either KRM-20 combined wi...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
AbstractProstate cancer is a candidate for immunotherapy because cancer cells express tissue-specific proteins that can be therapeutic targets. However, immune checkpoint inhibitors and active immunization have performed poorly in clinical trials. We developed a novel virus-like particle (VLP) vaccine composed of bovine papillomavirus L1 protein engineered to display surface docking sites. We decorated VLPs with peptides encoding T cell epitopes from two prostate cancer-associated tumor antigens, prostate stem cell antigen (PSCA), and prostatic acid phosphatase (PAP-1 and PAP-2), and a neo-antigen, stimulator of prostatic ...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
Abstract Immunotherapy is considered as an effective method for cancer treatment owing to the induction of specific and long-lasting anti-cancer effects. Immunotherapeutic strategies have shown significant success in human malignancies, particularly in prostate cancer (PCa), a major global health issue regarding its high metastatic rates. In fact, the first cancer vaccine approved by FDA was Provenge, which has been successfully used for treatment of PCa. Despite the remarkable success of cancer immunotherapy in PCa, many of the developed immunotherapy methods show poor therapeutic outcomes. Immunosuppression in t...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research
ONCOS-102, a promising immunotherapy vaccine, is moving closer to becoming a part of future first-line treatment for mesothelioma. Early clinical trial results announced this week show safety and efficacy when the vaccine is used in combination with standard-of-care chemotherapy for patients with inoperable pleural mesothelioma. Targovax, a Scandinavian pharmaceutical company developing the drug, is moving forward with another study combining ONCOS-102 with a checkpoint inhibitor drug such as Keytruda (pembrolizumab) or Opdivo (nivolumab), along with chemotherapy. “We have seen enough data at this point to be going ...
Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
In this study, we tested whether vaccinations with DCs, loaded with a PD-L1 immunogen (PDL1-Vax), are able to induce anti-PD-L1 immune responses. We found that DCs loaded with PDL1-Vax induced anti-PD-L1 antibody and T cell responses in immunized mice and that PD-L1-specific CTLs had cytolytic activities against PD-L1+ tumor cells. We demonstrated that vaccination with PDL1-Vax DCs potently inhibited the growth of PD-L1+ tumor cells. In summary, this study demonstrates for the first time the principle and feasibility of DC vaccination (PDL1-Vax) to actively induce anti-PD-L1 antibody and T cell responses capable of inhibit...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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
ConclusionsImmunotherapy with primary DC subsets induced functional antigen-specific T cells. The presence of functional antigen-specific T cells correlated with longer rPFS.Clinical trial identificationNCT02692976.Legal entity responsible for the studyJolanda de Vries and Winald Gerritsen.FundingThis work was supported by Stichting Afweer Tegen Kanker, Dr. Paul A.J. Speth Stichting and H2020 EU grant PROCROP (grant No 635122). Carl G. Figdor received ERC Adv Grant PATHFINDER (269019) and the NWO Spinoza grant. I. Jolanda M. de Vries received NWO-Vici grant (918.14.655).DisclosureAll authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Prostate cancer (PCa) is the most common cancer in men, and the second leading cause of cancer related death in men in Western countries. The standard therapy for metastatic PCa is androgen suppression therapy (AST). Men undergoing AST eventually develop metastatic castration-resistant prostate cancer (mCRPC), of which there are limited treatment options available. Immunotherapy has presented substantial benefits for many types of cancer, but only a marginal benefit for mCRPC, at least in part, due to the immunosuppressive tumor microenvironment (TME). Current clinical trials are investigating monotherapies or combination ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
AbstractPurpose of ReviewTo date, prostate cancer has been poorly responsive to immunotherapy. In the current review, we summarize and discuss the current literature on the use of vaccine therapy and checkpoint inhibitor immunotherapy in metastatic castration-resistant prostate cancer (mCRPC).Recent FindingsSipuleucel-T currently remains the only FDA-approved immunotherapeutic agent for prostate cancer. Single-agent phase 3 vaccine trials with GVAX and PROSTVAC have failed to demonstrate survival benefit to date. Clinical trials using combination approaches, including combination PROSTVAC along with a neoantigen vaccine an...
Source: Current Urology Reports - Category: Urology & Nephrology Source Type: research
Conclusion MTDH is pro-oncogenic factor playing multifaceted and diverse roles in cancer progression. Its association and central role in regulating signaling pathways such a MAPK, wnt/β-catenin, PI3K/AkT, NF-κβ pathways in various cancers shows that it plays a vital role in metastasis. MTDH contribution to chemo and radiotherapy resistance provides a new direction for the development of anticancer therapeutics. Multiple mechanisms converge to promote expression of MTDH in cancers. Further studies are therefore warranted to determine whether the elevated MTDH expression has prognostic value for development...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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