Cancers, Vol. 11, Pages 1909: A Novel Anti-PD-L1 Vaccine for Cancer Immunotherapy and Immunoprevention

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 inhibiting PD-L1+ tumor growth. This novel anti-PD-L1 vaccination strategy could be used for cancer treatment and prevention.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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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
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
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
Clara Degos1, Mellie Heinemann2, Julien Barrou2, Nicolas Boucherit1, Eric Lambaudie2, Ariel Savina3†, Laurent Gorvel1* and Daniel Olive1* 1Tumor Immunology Team, IBISA Immunomonitoring Platform, Cancer Research Center of Marseillle, INSERM U1068, CNRS U7258, Institut Paoli-Calmettes, Aix-Marseille University, Marseille, France 2Department of Surgical Oncology 2, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, Marseille, France 3Institut Roche, Boulogne Billancourt, France Endometrial Cancer is the most common cancer in the female genital tract in developed countries, and with its ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions and Perspectives In this review, we have discussed important milestones from the early description of “Serum-sickness” as being due to antibodies directed against Neu5Gc epitopes all the way to the present-day therapeutic implications of these antibodies in cancer therapy. Some of these milestones have been represented in a concise timeline (Figure 6). While the “Xenosialitis” hypothesis is well-supported in the human-like mouse models, it has yet to be conclusively proven in humans. It remains to be seen if “Xenosialitis” plays a role in other uniquely-human diseases. FI...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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