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Immune based cancer therapy

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https://www.readbyqxmd.com/read/28079009/emerging-roles-of-calreticulin-in-cancer-implications-for-therapy
#1
Kavya Venkateswaran, Amit Verma, Anant Narayan Bhatt, Anju Shrivastava, Kailash Manda, Hanumantharao G Raj, Ashok Prasad, Christophe Len, Virinder S Parmar, Bilikere Dwarakanath
Calreticulin (CRT), initially identified as a ubiquitous calcium-binding protein in the endoplasmic reticulum, has emerged as a multifunctional protein with roles in calcium homeostasis, molecular chaperoning and cell adhesion. Emerging evidence suggests its involvement in tumorigenesis facilitating proliferation, migration, and adhesion. CRT translocated to the cell surface (ecto-CRT) serves as a phagocytic signal for immunogenic cell death (ICD) mediated through dendritic cells (DCs) and cytotoxic T-cell activation thereby making tumors susceptible to immunotherapy-based anti-cancer strategies...
January 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28077676/a-ptk7-targeted-antibody-drug-conjugate-reduces-tumor-initiating-cells-and-induces-sustained-tumor-regressions
#2
Marc Damelin, Alexander Bankovich, Jeffrey Bernstein, Justin Lucas, Liang Chen, Samuel Williams, Albert Park, Jorge Aguilar, Elana Ernstoff, Manoj Charati, Russell Dushin, Monette Aujay, Christina Lee, Hanna Ramoth, Milly Milton, Johannes Hampl, Sasha Lazetic, Virginia Pulito, Edward Rosfjord, Yongliang Sun, Lindsay King, Frank Barletta, Alison Betts, Magali Guffroy, Hadi Falahatpisheh, Christopher J O'Donnell, Robert Stull, Marybeth Pysz, Paul Escarpe, David Liu, Orit Foord, Hans Peter Gerber, Puja Sapra, Scott J Dylla
Disease relapse after treatment is common in triple-negative breast cancer (TNBC), ovarian cancer (OVCA), and non-small cell lung cancer (NSCLC). Therapies that target tumor-initiating cells (TICs) should improve patient survival by eliminating the cells that can drive tumor recurrence and metastasis. We demonstrate that protein tyrosine kinase 7 (PTK7), a highly conserved but catalytically inactive receptor tyrosine kinase in the Wnt signaling pathway, is enriched on TICs in low-passage TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28074285/t-cell-receptor-repertoire-usage-in-cancer-as-a-surrogate-marker-for-immune-responses
#3
REVIEW
David Schrama, Cathrin Ritter, Jürgen C Becker
Characterizing the interaction of cancer cells with the host adaptive immune system is critical for understanding tumor immunology and the modus operandi of immunotherapeutic interventions to treat cancer. As the key cellular effectors of adaptive immunity, T cells are endowed with specialized receptors (the T cell receptor; TCR), to recognize and to eliminate cancer cells. The diversity of the TCR repertoire results from specialized genetic diversification mechanisms that generate an incredible variability allowing recognizing extensive collections of antigens...
January 10, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28073842/expression-of-cd14-il-10-and-tolerogenic-signature-in-dendritic-cells-inversely-correlate-with-response-to-tarp-vaccination-in-prostate-cancer-patients
#4
Luciano Castiello, Marianna Sabatino, Jiaqiang Ren, Masaki Terabe, Hanh Khuu, Lauren V Wood, Jay A Berzofsky, David F Stroncek
PURPOSE: Despite the vast number of clinical trials conducted so far, Dendritic cell (DC)-based cancer vaccines have mostly shown unsatisfactory results. Factors and manufacturing procedures essential for these therapeutics to induce effective anti-tumor immune responses have yet to be fully characterized. We here aimed to identify DC markers correlating with clinical and immunological response in a prostate carcinoma vaccination regimen. EXPERIMENTAL DESIGN: We performed an extensive characterization of DCs used to vaccinate 18 prostate carcinoma patients enrolled in a pilot trial of TCR gamma alternate reading frame protein (TARP) peptide vaccination (NCT00908258)...
January 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28064385/review-of-yoga-therapy-during-cancer-treatment
#5
REVIEW
Suzanne C Danhauer, Elizabeth L Addington, Stephanie J Sohl, Alejandro Chaoul, Lorenzo Cohen
PURPOSE: Reviews of yoga research that distinguish results of trials conducted during (versus after) cancer treatment are needed to guide future research and clinical practice. We therefore conducted a review of non-randomized studies and randomized controlled trials of yoga interventions for children and adults undergoing treatment for any cancer type. METHODS: Studies were identified via research databases and reference lists. Inclusion criteria were the following: (1) children or adults undergoing cancer treatment, (2) intervention stated as yoga or component of yoga, and (3) publication in English in peer-reviewed journals through October 2015...
January 7, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28063980/plant-viral-nanoparticles-based-her2-vaccine-immune-response-influenced-by-differential-transport-localization-and-cellular-interactions-of-particulate-carriers
#6
Sourabh Shukla, Jay T Myers, Sarah E Woods, Xingjian Gong, Anna E Czapar, Ulrich Commandeur, Alex Y Huang, Alan D Levine, Nicole F Steinmetz
Cancer vaccines are designed to elicit an endogenous adaptive immune response that can successfully recognize and eliminate residual or recurring tumors. Such approaches can potentially overcome shortcomings of passive immunotherapies by generating long-lived therapeutic effects and immune memory while limiting systemic toxicities. A critical determinant of vaccine efficacy is efficient transport and delivery of tumor-associated antigens to professional antigen presenting cells (APCs). Plant viral nanoparticles (VNPs) with natural tropism for APCs and a high payload carrying capacity may be particularly effective vaccine carriers...
December 27, 2016: Biomaterials
https://www.readbyqxmd.com/read/28059852/immune-checkpoint-inhibitors-in-first-line-therapy-of-advanced-non-small-cell-lung-cancer
#7
Jordi Remon, Benjamin Besse
PURPOSE OF REVIEW: Evading immune destruction is a hallmark of cancer. The first therapeutic wave in immunotherapies comprised a series of monoclonal antibodies directed against the immune checkpoint molecules cytotoxic T-lymphocyte-associated protein 4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1) revolutionizing the therapeutic landscape of advanced non-small cell lung cancer. They were validated initially as second-line treatment, becoming the new standard of care...
January 3, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28059608/near-future-of-tumor-immunology-anticipating-resistance-mechanisms-to-immunotherapies-a-big-challenge-for-clinical-trials
#8
João Paulo Portela Catani, Sandy Adjemian, Rachel P Riechelmann, Bryan E Strauss
The success of immunotherapies brings hope for the future of cancer treatment. Even so, we are faced with a new challenge, that of understanding which patients will respond initially and, possibly, develop resistance. The examination of the immune profile, especially approaches related to the immunoscore, may foretell which tumors will have a positive initial response. Ideally, the mutation load would also be analysed, helping to reveal tumor associated antigens that are predictive of an effective cytolytic attack...
January 6, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28054442/markers-and-function-of-human-nk-cells-in-normal-and-pathological-conditions
#9
REVIEW
Genny Del Zotto, Emanuela Marcenaro, Paola Vacca, Simona Sivori, Daniela Pende, Mariella Della Chiesa, Francesca Moretta, Tiziano Ingegnere, Maria Cristina Mingari, Alessandro Moretta, And Lorenzo Moretta
Natural killer (NK) cells, the most important effectors of the Innate Lymphoid Cells (ILCs), play a fundamental role in tumor immune-surveillance, defense against viruses and, in general, in innate immune responses. NK cell activation is mediated by several activating receptors and co-receptors able to recognize ligands on virus-infected or tumor cells. To prevent healthy cells from auto-aggression, NK cells are provided with strong inhibitory receptors (KIRs and NKG2A) which recognize HLA class I molecules on target cells and, sensing their level of expression, allow killing of targets underexpressing HLA-class I...
January 5, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28053943/novel-oncolytic-viral-therapies-in-patients-with-thoracic-malignancies
#10
REVIEW
Zeeshan Ahmad, Robert A Kratzke
Oncolytic virotherapy is the use of replication-competent viruses to treat malignancies. The potential of oncolytic virotherapy as an approach to cancer therapy is based on historical evidence that certain viral infections can cause spontaneous remission of both hematologic and solid tumor malignancies. Oncolytic virotherapy may eliminate cancer cells through either direct oncolysis of infected tumor cells or indirect immune-mediated oncolysis of uninfected tumor cells. Recent advances in oncolytic virotherapy include the development of a wide variety of genetically attenuated RNA viruses with precise cellular tropism and the identification of cell-surface receptors that facilitate viral transfer to the tissue of interest...
2017: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/28053626/expression-of-t-lymphocyte-markers-in-human-epidermal-growth-factor-receptor-2-positive-breast-cancer
#11
Changro Lee, Seho Park, Joo Heung Kim, Sung Mook Lim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park
PURPOSE: The present study aimed to examine the clinical implications of CD4, CD8, and FOXP3 expression on the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer using a web-based database, and to compare the immunohistochemical expression of T-lymphocyte markers using primary and metastatic HER2-positive tumor tissues before and after HER2-targeted therapy. METHODS: Using the cBioPortal for Cancer Genomics and Kaplan-Meier plotter, the mRNA expression, association between T-lymphocyte markers, and survival in HER2-positive cancers were investigated according to various cutoff levels...
December 2016: Journal of Breast Cancer
https://www.readbyqxmd.com/read/28043608/new-options-in-tuberculosis-care-visions-for-the-future-are-crucial-for-controlling-the-disease
#12
Malin Ridell
The current strategies for controlling tuberculosis (TB) are not sufficient. Improved prophylactic and diagnostic tools are imperative, being crucial for decreasing TB incidence and mortality and for preventing outbreaks. Furthermore, new and better drugs are badly needed, particularly considering the increase in cases with multidrug-resistant strains. The current TB vaccine-the Bacillus Calmette-Guérin vaccine-has a preventive impact on disseminated TB in children, but little effect on the most common form of TB, that is, lung TB in adults and young adults...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28043149/mesenchymal-stromal-cells-producing-tnf%C3%AE-lack-inhibitory-effect-against-a375-experimental-lung-metastasis
#13
S Tyciakova, M Matuskova, R Bohovic, L Kucerova
Cell-based anticancer therapy using mesenchymal stromal cells (MSCs) engineered to express therapeutic genes has a potential to target the cancer cells in vivo. Metastatic dissemination of melanoma remains a serious problem in the treatment. In our previous work we used MSCs overexpressing gene for tumor necrosis factor α (TNFα; MSCs/TNFα), and we achieved inhibition of melanoma xenograft growth when engineered MCSs/TNFα were coinjected with tumor cells subcutaneously. The TNFα as a pleiotropic cytokine induces apoptosis of tumor cells, creates "tumor resistant" microenvironment, enhances immune response and can have tumor destructive capacity in selected tumor types, especially in tumors of mesodermal origin...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28042949/recombinant-parvoviruses-armed-to-deliver-cxcl4l1-and-cxcl10-are-impaired-in-their-antiangiogenic-and-antitumoral-effects-in-a-kaposi-sarcoma-tumor-model-due-to-the-chemokines-interference-with-the-virus-cycle
#14
Christiane Dinsart, Kalliopi Pervolaraki, Alexandra Stroh-Dege, Muriel Lavie, Isabelle Ronsse, Jean Rommelaere, Jo Van Damme, Katrien Van Raemdonck, Sofie Struyf
Application of oncolytic viruses is a valuable option to broaden the armament of anti-cancer therapies as these combine specific cytotoxic effects and immune-stimulating properties. The self-replicating H-1 parvovirus (H-1PV) is a prototypical oncolytic virus that besides targeting tumor cells also infects endothelial cells, thus combining oncolytic and angiostatic traits. To increase its therapeutic value, H-1PV can be armed with cytokines or chemokines to enhance the immunological response. Some chemokines, more specifically the CXCR3 ligands CXCL4L1 and CXCL10 combine immune-stimulating properties with angiostatic activity...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28042779/antibody-delivery-mediated-by-recombinant-adeno-associated-virus-for-the-treatment-of-chronic-and-infectious-diseases
#15
Marc-André Robert, Rénald Gilbert, Bruno Gaillet
Monoclonal antibodies (mAbs) based-therapies are currently one of the most successful strategies to treat immune disorders, cancer and infectious diseases. Vectors derived from adeno-associated virus (AAV) are very attractive to deliver the genes coding the mAbs because they allow long-term expression thus, reducing the number of administrations. They can also penetrate biological barriers such as the blood-brain-barrier to transduce cells localized in immunoprivileged organs. Recent animal studies with AAV have demonstrated the capacity of AAV to deliver sufficient quantity of antibodies to confer an efficient immunoprotection against chronic and infectious diseases for several months to years...
January 2, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28040549/increased-peripheral-cd4-regulatory-t-cells-persist-after-successful-direct-acting-antiviral-treatment-of-chronic-hepatitis-c
#16
Bettina Langhans, Hans Dieter Nischalke, Benjamin Krämer, Annekristin Hausen, Leona Dold, Peer van Heteren, Robert Hüneburg, Jacob Nattermann, Christian P Strassburg, Ulrich Spengler
INTRODUCTION: CD4(+) regulatory T cells (Tregs) expand during chronic hepatitis C virus (HCV) infection, inhibit antiviral immunity and promote fibrosis. Directly acting antivirals (DAA) have revolutionized HCV therapy. However, it is unclear if Tregs are normalized after DAA-induced HCV elimination. METHODS: We analyzed Tregs before (=baseline), at end of therapy (EOT), 12 and 24 weeks (SVR12, SVR24) and long-term (51±14 weeks) after EOT in 26 genotype-1-infected patients successfully treated with sofosbuvir (SOF) plus IFN/ribavirin (n=12) and IFN-free DAA regimens (SOF plus daclatasvir or simeprevir; n=14)...
December 28, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28030901/radiotherapy-and-immune-checkpoint-blockades-a-snapshot-in-2016
#17
REVIEW
Taeryool Koo, In Ah Kim
Immune checkpoint blockades including monoclonal antibodies (mAbs) of cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) have been emerged as a promising anticancer therapy. Several immune checkpoint blockades have been approved by US Food and Drug Administration (FDA), and have shown notable success in clinical trials for patients with advanced melanoma and non-small cell lung cancer. Radiotherapy is a promising combination partner of immune checkpoint blockades due to its potent pro-immune effect...
December 2016: Radiation Oncology Journal
https://www.readbyqxmd.com/read/28030784/dutch-melanoma-treatment-registry-quality-assurance-in-the-care-of-patients-with-metastatic-melanoma-in-the-netherlands
#18
Anouk Jochems, Maartje G Schouwenburg, Brenda Leeneman, Margreet G Franken, Alfons J M van den Eertwegh, John B A G Haanen, Hans Gelderblom, Carin A Uyl-de Groot, Maureen J B Aarts, Franchette W P J van den Berkmortel, Willeke A M Blokx, Mathilde C Cardous-Ubbink, Gerard Groenewegen, Jan Willem B de Groot, Geke A P Hospers, Ellen Kapiteijn, Rutger H Koornstra, Wim H Kruit, Marieke W Louwman, Djura Piersma, Rozemarijn S van Rijn, Albert J Ten Tije, Gerard Vreugdenhil, Michel W J M Wouters, Jacobus J M van der Hoeven
BACKGROUND: In recent years, the treatment of metastatic melanoma has changed dramatically due to the development of immune checkpoint and mitogen-activated protein (MAP) kinase inhibitors. A population-based registry, the Dutch Melanoma Treatment Registry (DMTR), was set up in July 2013 to assure the safety and quality of melanoma care in the Netherlands. This article describes the design and objectives of the DMTR and presents some results of the first 2 years of registration. METHODS: The DMTR documents detailed information on all Dutch patients with unresectable stage IIIc or IV melanoma...
December 25, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/28028314/redirecting-t-cells-to-eradicate-b-cell-acute-lymphoblastic-leukemia-bispecific-t-cell-engagers-and-chimeric-antigen-receptors
#19
REVIEW
I Aldoss, R C Bargou, D Nagorsen, G R Friberg, P A Baeuerle, S J Forman
Recent advances in antibody technology to harness T-cells for cancer immunotherapy, particularly in the difficult-to-treat setting of relapsed or refractory acute lymphoblastic leukemia (r/r ALL), has led to innovative methods for directing cytotoxic T-cells to specific surface antigens on cancer cells. One approach involves administration of soluble bispecific (or dual-affinity) antibody-based constructs that temporarily bridge T-cells and cancer cells. Another approach infuses ex vivo-engineered T-cells that express a surface plasma membrane-inserted antibody construct called a chimeric antigen receptor (CAR)...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28027646/protein-nanocage-mediated-fibroblast-activation-protein-targeted-photoimmunotherapy-to-enhance-cytotoxic-t-cell-infiltration-and-tumor-control
#20
Zipeng Zhen, Wei Tang, Mengzhe Wang, Shiyi Zhou, Hui Wang, Zhanhong Wu, Zhonglin Hao, Zibo Li, Lin Liu, Jin Xie
Carcinoma-associated fibroblasts (CAFs) are found in many types of cancer and play an important role in tumor growth and metastasis. Fibroblast-activation protein (FAP), which is overexpressed on the surface of CAFs, has been proposed as a universal tumor targeting antigen. However, recent studies show that FAP is also expressed on multipotent bone marrow stem cells. A systematic anti-FAP therapy may lead to severe side effects and even death. Hence, there is an urgent need of a therapy that can selectively kill CAFs without causing systemic toxicity...
January 4, 2017: Nano Letters
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