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Anti cancer peptide

Shabnam Shaabani, Harmen P S Huizinga, Roberto Butera, Ariana Kouchi, Katarzyna Guzik, Katarzyna Magiera-Mularz, Tad A Holak, Alexander Dömling
The protein protein interaction PD1/PD-L1 is an important immune checkpoint and several recently approved monoclonal antibodies show promising anti cancer activities in the clinical practice. However, only a small percentage of cancer patients benefit from PD1/PD-L1 directed mAbs. Moreover, some patients experience immune related side effects upon treatment with these mAbs. Recently, several atomic-resolution structures of human PD1/PD-L1, and small molecules, peptides and mAbs with PD-L1 and PD1 open the field for structure based drug design...
August 14, 2018: Expert Opinion on Therapeutic Patents
Adi Sharbi-Yunger, Mareike Grees, Cafri Gal, David Bassan, Stefan B Eichmüller, Esther Tzehoval, Jochen Utikal, Viktor Umansky, Lea Eisenbach
For many years, clinicians and scientists attempt to develop methods to stimulate the immune system to target malignant cells. Recent data suggest that effective cancer vaccination requires combination immunotherapies to overcome tumor immune evasion. Through presentation of both MHC-I and II molecules, DCs based vaccine platforms are effective in generating detectable CD4 and CD8 T cell responses against tumor associated antigens. Several platforms include DC transfection with mRNA of the desired tumor antigen...
August 14, 2018: International Journal of Cancer. Journal International du Cancer
Adina Elena Stanciu, Marcel Marian Stanciu, Radu Gabriel Vatasescu
PURPOSE: Heart failure (HF) is considered to be a complex syndrome associated with neurohormonal and cytokine activation, that contribute to its progression. There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor marker widely used for ovarian cancer therapy monitoring, was significantly elevated in HF patients. We hypothesized that inflammatory stimuli may be responsible for amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and CA-125 production and release in chronic HF (CHF)...
August 8, 2018: Cytokine
Jun Ishihara, Ako Ishihara, Lambert Potin, Peyman Hosseinchi, Kazuto Fukunaga, Martina Damo, Thomas F Gajewski, Melody A Swartz, Jeffrey A Hubbell
CD40 is an immune co-stimulatory receptor expressed by antigen-presenting cells. Agonistic anti-CD40 antibodies have demonstrated considerable anti-tumor effects yet can also elicit serious treatment-related adverse events, such as liver toxicity, including in man. We engineered a variant that binds extracellular matrix through a super-affinity peptide derived from placenta growth factor-2 (PlGF-2123-144) to enhance anti-CD40's effects when administered locally. Peri-tumoral injection of PlGF-2123-144-anti-CD40 antibody showed prolonged tissue retention at the injection site and substantially decreased systemic exposure, resulting in decreased liver toxicity...
August 10, 2018: Molecular Cancer Therapeutics
Justin H Lo, Liangliang Hao, Mandar D Muzumdar, Srivatsan Raghavan, Ester J Kwon, Emilia M Pulver, Felicia Hsu, Andrew J Aguirre, Brian M Wolpin, Charles S Fuchs, William C Hahn, Tyler Jacks, Sangeeta N Bhatia
Pancreatic cancer is one of the leading causes of cancer death, with 5-year survival of 8.5%. The lack of significant progress in improving therapy reflects our inability to overcome the desmoplastic stromal barrier in pancreatic ductal adenocarcinoma (PDAC) as well as a paucity of new approaches targeting its genetic underpinnings. RNA interference holds promise in targeting key mutations driving PDAC; however, a nucleic acid delivery vehicle that homes to PDAC and breaches the stroma does not yet exist. Noting that the cyclic peptide iRGD mediates tumor targeting and penetration through interactions with αvβ3/5 integrins and neuropilin-1, we hypothesized that "tandem" peptides combining a cell-penetrating peptide and iRGD can encapsulate siRNA to form tumor-penetrating nanocomplexes (TPNs) capable of delivering siRNA to PDAC...
August 10, 2018: Molecular Cancer Therapeutics
Wei Xie, Yan Zhang, Yuan He, Kunchi Zhang, Guoqing Wan, Yanjuan Huang, Zhaoli Zhou, Gang Huang, Jin Wang
Triple negative breast cancer (TNBC) is one of the most difficult malignancy to treat due to a lack of targeted therapy. Studies have demonstrated that the activation of Wnt/β-catenin signaling was preferentially found in TNBC. Frizzled-7 (Fzd7), one of the Wnt receptors, was significantly up-regulated in TNBC and modulated TNBC tumorigenesis through the Wnt signaling pathway, indicating Fzd7 is a biomarker and a potential therapeutic target for TNBC. Here, we designed a recombinant soluble peptide fragment (rhFzd7) to antagonize Fzd7 by competitively binding with Wnt ligands...
August 7, 2018: International Journal of Biochemistry & Cell Biology
Xiao-Yan He, Bo-Ya Liu, Chang Xu, Ren-Xi Zhuo, Si-Xue Cheng
To achieve effective tumor eradication using anti-tumor immunotherapies, a fusion peptide functionalized gene delivery system for macrophage and tumor targeting delivery of the plasmid DNA encoding the IL-12 gene (pDNA IL-12) was prepared for macrophage re-polarization as well as reversal of cancer immunosuppression. A fusion peptide containing the tuftsin sequence that can interact with Fc receptors and neuropilin-1, and hyaluronic acid (HA) that can interact with CD44 were introduced into the delivery system by self-assembly to form peptide/hyaluronic acid/protamine/CaCO3/DNA nanoparticles (PHNP) with both macrophage targeting and tumor targeting capabilities...
August 9, 2018: Nanoscale
Judith Guasch, Marco Hoffmann, Jennifer Diemer, Hossein Riahinezhad, Stefanie Neubauer, Horst Kessler, Joachim P Spatz
Adoptive cell therapies are showing very promising results in the fight against cancer. However, these therapies are expensive and technically challenging in part due to the need of a large number of specific T cells, which must be activated and expanded in vitro. Here we describe a method to activate primary human T cells using a combination of nanostructured surfaces functionalized with the stimulating anti-CD3 antibody and the peptidic sequence arginine-glycine-aspartic acid, as well as costimulatory agents (anti-CD28 antibody and a cocktail of phorbol 12-myristate 13-acetate, ionomycin, and protein transport inhibitors)...
August 8, 2018: Nano Letters
Matthieu Desroses, Sander Busker, Juan Astorga-Wells, Sanaz Attarha, Iryna Kolosenko, Roman A Zubarev, Thomas Helleday, Dan Grandér, Brent D G Page
STAT3 protein is an established target for the development of new cancer therapeutic agents. Despite lacking a traditional binding site for small molecule inhibitors, many STAT3 inhibitors have been identified and explored for their anti-cancer activity. Because STAT3 signaling is mediated by protein-protein interactions, indirect methods are often employed to determine if proposed STAT3 inhibitors bind to STAT3 protein. While established STAT3 inhibition assays (such as the fluorescence polarization assay, electrophoretic mobility shift assay and ELISAs) have been used to identify novel inhibitors of STAT3 signaling, methods that directly assess STAT3 protein-inhibitor interactions could facilitate the development of novel inhibitors...
July 17, 2018: Journal of Pharmaceutical and Biomedical Analysis
Amanda Abbott, Christopher G Sakellis, Eric Andersen, Yuji Kuzuhara, Lauren Gilbert, Kelly Boyle, Matthew H Kulke, Jennifer A Chan, Heather A Jacene, Annick D Van den Abbeele
[Lutetium-177-DOTA(0),Tyr(3)]octreotate (177 Lu-DOTATATE) is a radiolabeled somatostatin analog that has been approved by the U.S. Food and Drug Administration for the treatment of somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors in adults. Radionuclide therapies have been administered for many years within nuclear medicine departments in North America. However, in comparison to other radiotherapies, 177 Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) involves more planning, coordination, concomitant medication administration (anti-emetic medications and amino acids) and direct patient care...
August 3, 2018: Journal of Nuclear Medicine Technology
Sönke Detlefsen, Jesper D de Vos, Julia T Tanassi, Niels H H Heegaard, Claus Fristrup, Ove B Schaffalitzky de Muckadell
The diagnosis of autoimmune pancreatitis (AIP) and its differential diagnosis from pancreatic cancer (PC) can be challenging. In this retrospective study, we aimed to evaluate the value of anti-plasminogen binding peptide (a-PBP), immunoglobulin G4 (IgG4), and anti-carbonic anhydrase-II (a-CA-II), together with other serological markers whose value is not fully elucidated.The serum levels of a-PBP, IgG4, IgG, anti-nuclear antibodies (ANA), anti-lactoferrin (a-LF), a-CA-II, and rheumatoid factor (RF) were evaluated in patients with AIP (n = 29), PC (n = 17), pancreatic neuroendocrine neoplasm (P-NEN, n = 12), and alcoholic chronic pancreatitis (ACP, n = 41)...
August 2018: Medicine (Baltimore)
Lidija Covic, Athan Kuliopulos
The G-protein coupled receptors (GPCRs) belong to a large family of diverse receptors that are well recognized as pharmacological targets. However, very few of these receptors have been pursued as oncology drug targets. The Protease-activated receptor 1 (PAR1), which is a G-protein coupled receptor, has been shown to act as an oncogene and is an emerging anti-cancer drug target. In this paper, we provide an overview of PAR1's biased signaling role in metastatic cancers of the breast, lungs, and ovaries and describe the development of PAR1 inhibitors that are currently in clinical use to treat acute coronary syndromes...
July 31, 2018: International Journal of Molecular Sciences
Ahmad Noei, Amir Nili-Ahmadabadi, Meysam Soleimani
BACKGROUNDS: Peptide-based drugs have shown promising results in overcoming the limitations of chemotherapeutic drugs by providing a targeted therapy approach to cancer. However, the response rate of targeted therapies is limited, in large part due to the intra- and inter-heterogeneity of tumors. METHODS: In this study, we engineered a novel chimeric protein composed of the p28 peptide as a tumor-homing killer peptide and apoptin as a killer peptide. We evaluated its cytotoxicity against MCF7 and MDA-MB-231 breast cancer cells and HEK-293 normal cells by the MTT assay...
July 30, 2018: Drug Research
Yan Wang, Qiong Lei, Zheng Yan, Cangjie Shen, Nan Wang
TRAIL, a promising antitumor immuno-agent, exerted limited efficacy in clinical trials. The third disulfide loop of TGF-α (TGF3L peptide) with a very low affinity for EGFR has been reported to enhance the activity of fused antigens or cytokines. We wondered whether fusion of this peptide could enhance TRAIL activity and what the underlying mechanism for this enhancement would be. The TGF3L-TRAIL showed greatly enhanced cytotoxicity in a variety of cancer cell lines while spared normal cells unharmed. Typical apoptosis and cellular caspase activation were potently induced by TGF3L-TRAIL at the concentration levels corresponding to its cytotoxicity...
July 27, 2018: Biochemical Pharmacology
Fatah B Ahtesh, Lily Stojanovska, Vasso Apostolopoulos
The development of agricultural products as well as the industrialization of food production have led to dramatic lifestyle changes, particularly in dietary patterns, which in turn has increased the occurrence of chronic diseases and hypertension. In order to help overcome this, the food industry has developed functional milk products. Milk products, particularly fermented milk containing probiotics, are popular. Probiotics may promote gut health, reduce allergenicity, increase the bio-accessibility of fats/proteins in foods, and lower blood pressure because they contain poly-amines and bioactive peptides...
September 2018: Maturitas
Björn Stolte, Amanda Balboni Iniguez, Neekesh V Dharia, Amanda L Robichaud, Amy Saur Conway, Ann M Morgan, Gabriela Alexe, Nathan J Schauer, Xiaoxi Liu, Gregory H Bird, Aviad Tsherniak, Francisca Vazquez, Sara J Buhrlage, Loren D Walensky, Kimberly Stegmaier
Ewing sarcoma is a pediatric cancer driven by EWS-ETS transcription factor fusion oncoproteins in an otherwise stable genomic background. The majority of tumors express wild-type TP53 , and thus, therapies targeting the p53 pathway would benefit most patients. To discover targets specific for TP53 wild-type Ewing sarcoma, we used a genome-scale CRISPR-Cas9 screening approach and identified and validated MDM2 , MDM4 , USP7, and PPM1D as druggable dependencies. The stapled peptide inhibitor of MDM2 and MDM4, ATSP-7041, showed anti-tumor efficacy in vitro and in multiple mouse models...
August 6, 2018: Journal of Experimental Medicine
Yasushi Akahori, Linan Wang, Motohiro Yoneyama, Naohiro Seo, Satoshi Okumura, Yoshihiro Miyahara, Yasunori Amaishi, Sachiko Okamoto, Junichi Mineno, Hiroaki Ikeda, Takehiro Maki, Hiroshi Fujiwara, Yoshiki Akatsuka, Takuma Kato, Hiroshi Shiku
The recent success of chimeric antigen receptor (CAR)-T cell therapy for treatment of hematologic malignancies supports further development of treatments for both liquid and solid tumors. However, expansion of CAR-T cell therapy is limited by the availability of surface antigens specific for the tumor while sparing normal cells. There is a rich diversity of tumor antigens from intracellularly expressed proteins that current and conventional CAR-T cells are unable to target. Furthermore, adoptively transferred T cells often suffer from exhaustion and insufficient expansion, in part, due to the immunosuppressive mechanisms operating in tumor-bearing hosts...
July 25, 2018: Blood
Allan Wee Ren Ng, Pei Jun Tan, Winfrey Pui Yee Hoo, Dek Shen Liew, Michelle Yee Mun Teo, Pui Yan Siak, Sze Man Ng, Ee Wern Tan, Raha Abdul Rahim, Renee Lay Hong Lim, Adelene Ai Lian Song, Lionel Lian Aun In
Background: Somatic point substitution mutations in the KRAS proto-oncogene primarily affect codons 12/13 where glycine is converted into other amino acids, and are highly prevalent in pancreatic, colorectal, and non-small cell lung cancers. These cohorts are non-responsive to anti-EGFR treatments, and are left with non-specific chemotherapy regimens as their sole treatment options. In the past, the development of peptide vaccines for cancer treatment was reported to have poor AT properties when inducing immune responses...
2018: PeerJ
Zinaida A Dubeykovskaya, Phaneendra Kumar Duddempudi, Huan Deng, Giovanni Valenti, Krystle L Cuti, Karan Nagar, Yagnesh Tailor, Chandan Guha, Jan Kitajewski, Timothy C Wang
TFF2 is a small, secreted protein with anti-inflammatory properties. We previously have shown that TFF2 gene delivery via adenovirus (Ad-Tff2) suppresses colon tumor growth in colitis associated cancer. Therefore, systemic administration of TFF2 peptide could potentially provide a similar benefit. Because TFF2 shows a poor pharmacokinetic, we sought to modify the TFF2 peptide in a manner that would lower its clearance rate but retain bioactivity. Given the absence of a sequence-based prediction of TFF2 functionality, we chose to genetically fuse the C-terminus of TFF2 with the carboxyl-terminal peptide of human chorionic gonadotropin β subunit, and inserted into adenoviral vector that expresses Flag...
July 25, 2018: Cancer Gene Therapy
Kie Honjo, Taiji Hamada, Takuya Yoshimura, Seiya Yokoyama, Sohsuke Yamada, Yan-Qin Tan, Lai K Leung, Norifumi Nakamura, Yasuyo Ohi, Michiyo Higashi, Akihide Tanimoto
The Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is a novel breast cancer cell expressing peptide, originally found in the neural cells as an anti-apoptotic factor, could inhibit cell apoptosis and enhance cell migration and invasion in human breast cancer cell lines. The expression of PCP4/PEP19 is induced by estrogens in estrogen receptor-positive (ER+ ) MCF-7 cells but also highly expressed in ER- SK-BR-3 cells. In this study, we investigated the effects of PCP4/PEP19 on aromatase gene expression in MCF-7 and SK-BR-3 human breast cancer cells...
July 3, 2018: Oncotarget
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