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T cell cancer therapy

Gang Wang, Yu-Zhu Wang, Yang Yu, Jun-Jie Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Studies have shown that the etiology and pathogenesis of colorectal cancer are closely related to the tumor microenvironment, and the cancer tissue is still in the state of "energy deficit" and has to promote energy generation through high glycolysis. Rhus chinensis Mill is a Chinese herbal medicine used to treat various types of solid tumors in China. Colorectal cancer (CRC) is a heterogeneous disease group caused by abnormal changes in glucose metabolism resulted in lactic acid production, which remodels acidosis...
February 14, 2019: Journal of Ethnopharmacology
Reina Mizuno, Takumi Maruhashi, Daisuke Sugiura, Kenji Shimizu, Mizuki Watada, Il-Mi Okazaki, Taku Okazaki
Cancer immunotherapies targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 revolutionized cancer treatment and instigated various trials to develop new cancer immunotherapies with higher therapeutic efficacy. Agonistic Abs against tumor necrosis factor receptor super family (TNFRSF) molecules are highly expected due to their high potential to enhance survival, proliferation, and effector function of T cells. To date, agonistic antibodies (Abs) against CD27, GITR, OX40, and 4-1BB have been reported to increase the efficacy of anti-PD-1 therapy in animal models and clinical trials of these combinatorial therapies are underway...
February 13, 2019: Biochemical and Biophysical Research Communications
David G Leach, Simon Young, Jeffrey D Hartgerink
Macroscale biomaterials, such as preformed implantable scaffolds and injectable soft materials, possess powerful synergies with anti-cancer immunotherapies. Immunotherapies on their own typically have poor delivery properties, and often require repeated high-dose injections that result in serious off-tumor effects and/or limited efficacy. Rationally designed biomaterials allow for discrete localization and controlled release of immunotherapeutic agents, and have been shown in a large number of applications to improve outcomes in the treatment of cancers via immunotherapy...
February 13, 2019: Acta Biomaterialia
Jong Woo Lee, Yu Zhang, Kyung Jin Eoh, Roshan Sharma, Miguel F Sanmamed, Jenny Wu, Justin Choi, Hee Sun Park, Akiko Iwasaki, Edward Kaftan, Lieping Chen, Vali Papadimitrakopoulou, Roy S Herbst, Ja Seok Koo
PURPOSE: To characterize the tumor-infiltrating immune cells population in Kras/p53-driven lung tumors and to evaluate the combinatorial anti-tumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed cell death protein-1 (PD-1) or programmed cell death protein ligand 1 (PD-L1) in vivo. EXPERIMENTAL DESIGN: Trp53FloxFlox ;KrasG12D/+ ;Rosa26LSL-Luciferase/LSL-Luciferase (PKL) genetically engineered mice were utilized to develop autochthonous lung tumors with intratracheal delivery of adenoviral Cre recombinase...
February 13, 2019: Journal of Thoracic Oncology
Cecilia Roux, Soode Moghadas Jafari, Rahul Shinde, Gordon Duncan, David W Cescon, Jennifer Silvester, Mandy F Chu, Kelsey Hodgson, Thorsten Berger, Andrew Wakeham, Luis Palomero, Mar Garcia-Valero, Miguel A Pujana, Tak W Mak, Tracy L McGaha, Paola Cappello, Chiara Gorrini
The combination of immune checkpoint blockade with chemotherapy is currently under investigation as a promising strategy for the treatment of triple negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) are the most prominent component of the breast cancer microenvironment because they influence tumor progression and the response to therapies. Here we show that macrophages acquire an immunosuppressive phenotype and increase the expression of programmed death ligand-1 (PD-L1) when treated with reactive oxygen species (ROS) inducers such as the glutathione synthesis inhibitor, buthionine sulphoximine (BSO), and paclitaxel...
February 15, 2019: Proceedings of the National Academy of Sciences of the United States of America
Hampartsoum B Barsoumian, Lalit Batra, Pradeep Shrestha, William S Bowen, Hong Zhao, Nejat K Egilmez, Jorge G Gomez-Gutierrez, Esma S Yolcu, Haval Shirwan
: Costimulation through 4-1BB (CD137) receptor generates robust CD8+ T-effector and memory responses. The only known ligand, 4-1BBL, is a trimeric transmembrane protein that has no costimulatory activity as a soluble molecule. Thus, agonistic antibodies to the receptor have been used for cancer immunotherapy in preclinical models and are currently being evaluated in the clinic. Here, we report that treatment with an oligomeric form of the ligand, SA-4-1BBL, as a single agent is able to protect mice against subsequent tumor challenge irrespective of the tumor type...
February 15, 2019: Cancer Research
Carmen Criscitiello, Giulia Viale, Giuseppe Curigliano
The immune system plays a dual role of host-protecting and tumor-promoting, as elegantly expressed by the 'cancer immunoediting' hypothesis. Although breast cancer has not been traditionally considered to be immunogenic, recently there is accumulating and solid evidence on the association between immune system and breast cancer. To mount an effective anti-tumor response, host immunosurveillance must recognize tumor-specific epitopes, thus defining the antigenicity of a tumor. Neoantigens are mutant cancer peptides that arise as terminal products of the expression of somatic cancer mutations...
February 7, 2019: Breast: Official Journal of the European Society of Mastology
Jasmine Kaur, Abdelkader Daoud, Scott T Eblen
BACKGROUND: Epigenetic alterations comprise key regulatory events that dynamically alter gene expression and their deregulation is commonly linked to the pathogenesis of various diseases, including cancer. Unlike DNA mutations, epigenetic alterations involve modifications to proteins and nucleic acids that regulate chromatin structure without affecting the underlying DNA sequence, altering the accessibility of the transcriptional machinery to the DNA, thus modulating gene expression. In cancer cells, this often involves the silencing of tumor suppressor genes or the increased expression of genes involved in oncogenesis...
February 14, 2019: Current Molecular Pharmacology
Hisataka Kobayashi
Near infrared photoimmunotherapy(NIR-PIT)is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IRDye700DX(IR700), to a monoclonal antibody(mAb)targeting cell-surface molecules. NIR-PIT targetingEGFR usingthe cetuximab-IR700 conjugate is now in transition to fast-track global Phase Ⅲ clinical trial in late-stage head and neck squamous cell cancer patients. When exposed to NIR light, the conjugate induces a highlyselective necrotic/immunogenic cell death(ICD)only in target-positive, mAb-IR700-bound cancer cells...
January 2019: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Sherene Loi, Anita Giobbie-Hurder, Andrea Gombos, Thomas Bachelot, Rina Hui, Giuseppe Curigliano, Mario Campone, Laura Biganzoli, Hervé Bonnefoi, Guy Jerusalem, Rupert Bartsch, Manuela Rabaglio-Poretti, Roswitha Kammler, Rudolf Maibach, Mark J Smyth, Angelo Di Leo, Marco Colleoni, Giuseppe Viale, Meredith M Regan, Fabrice André
BACKGROUND: HER2-positive breast cancers usually contain large amounts of T-cell infiltrate. We hypothesised that trastuzumab resistance in HER2-positive breast cancer could be mediated by immune mechanisms. We assessed the safety and anti-tumour activity of pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, added to trastuzumab in trastuzumab-resistant, advanced HER2-positive breast cancer. METHODS: We did this single-arm, multicentre, phase 1b-2 trial in 11 centres based in five countries...
February 11, 2019: Lancet Oncology
M Slavik, T Kazda, I Selingerová, J Šána, P Ahmad, D Gurín, M Hermanová, T Novotný, R Červená, R Dymáčková, P Burkoň, O Slabý, P Šlampa
BACKGROUND: Oropharyngeal squamous cell tumors associated with human papillomavirus infection (p16 positive tumors) have better prognosis than p16 negative tumors regardless of the more advanced stage of the disease. Tumor volume (GTVt+n) is generally an important factor affecting treatment results of ionizing radiation. The aim of this prospective non-randomized study is to evaluate the effect of tumor volume on the (chemo)radiation treatment results in a group of patients with p16 negative and p16 positive oropharyngeal tumors...
2019: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Miika Martikainen, Magnus Essand
Glioblastoma (GBM) is the most common type of primary brain tumor in adults. Despite recent advances in cancer therapy, including the breakthrough of immunotherapy, the prognosis of GBM patients remains dismal. One of the new promising ways to therapeutically tackle the immunosuppressive GBM microenvironment is the use of engineered viruses that kill tumor cells via direct oncolysis and via stimulation of antitumor immune responses. In this review, we focus on recently published results of phase I/II clinical trials with different oncolytic viruses and the new interesting findings in preclinical models...
February 5, 2019: Cancers
Daniel Worroll, Giuseppe Galletti, Ada Gjyrezi, David Nanus, Scott T Tagawa, Paraskevi Giannakakou
Androgen receptor (AR) signaling drives prostate cancer (PC) progression and remains active upon transition to castration resistant prostate cancer (CRPC). Active AR signaling is achieved through the nuclear accumulation of AR following ligand binding and through expression of ligand-independent, constitutively active AR splice variants, such as AR-V7, which is the most commonly expressed variant in metastatic CRPC patients. Most currently approved PC therapies aim to abrogate AR signaling and activity by inhibiting this ligand-mediated nuclear translocation...
February 14, 2019: Physical Biology
Tobias A Mattei, Carlos R Goulart, Shawn S Rai, Azeem A Rehman, Michelle Williams, Ehud Mendel
BACKGROUND: Previous studies have described the association of spinal epidural lipomatosis with several conditions including chronic steroid therapy, Cushing's syndrome, obesity, Paget's disease, and hypothyroidism. We present a report of rapid development of spinal epidural lipomatosis after treatment with second-generation anti-androgen therapy, a new strategy for treatment of metastatic castration-resistant prostate cancer which has been increasingly employed in the past few years...
February 11, 2019: World Neurosurgery
Neelam Mukherjee, Karen M Wheeler, Robert S Svatek
PURPOSE OF REVIEW: Bacillus Calmette-Guérin (BCG) is the standard immune therapy for nonmuscle invasive bladder cancer. A systematic review of published articles regarding BCG treatment of bladder cancer was conducted and a commentary of these is provided to gain a perspective of the current major developments in the field. RECENT FINDINGS: Several BCG strains are utilized worldwide. As the understanding of genetic and phenotypic differences in these strains is elucidated, inquiries into the potential clinical effects of these various strains have been studied...
February 11, 2019: Current Opinion in Urology
Xiaoping Yang, Aliaa E M Daifallah, Shiela Shankar, Jacob Beer, Christine Marshall, Tzvete Dentchev, Francesca Seykora, Sebastian D'Armas, Jaeyi Hahn, Vivian Lee, Hanan H Sabry, Assem M Farag, John T Seykora
Actinic keratoses (AKs) and squamous cell carcinoma in situ (SCCIS) are precursor lesions for cutaneous squamous cell carcinoma (cSCC), the second most common form of cancer. Current topical therapies for AKs and SCCIS promote skin inflammation to eradicate lesions and do not directly target the biological mechanisms driving growth. We hypothesized that topical small molecule inhibitors targeting kinases promoting keratinocyte growth in AKs and SCCIS could induce regression of these lesions with less inflammation...
February 14, 2019: Experimental Dermatology
Yinan Yuan, Valeria Arcucci, Sidney M Levy, Marc G Achen
The debilitating condition known as secondary lymphedema frequently occurs after lymphadenectomy and/or radiotherapy for the treatment of cancer. These therapies can damage lymphatic vessels leading to edema, fibrosis, inflammation and dysregulated adipogenesis, which result in profound swelling of an affected limb. Importantly, lymphedema patients often exhibit impaired immune function which predisposes them to a variety of infections. It is known that lymphadenectomy can compromise the acquisition of adaptive immune responses and antibody production; however the cellular mechanisms involved are poorly understood...
2019: Frontiers in Immunology
Sunil Singhal, Jason Stadanlick, Michael J Annunziata, Abhishek S Rao, Pratik S Bhojnagarwala, Shaun O'Brien, Edmund K Moon, Edward Cantu, Gwenn Danet-Desnoyers, Hyun-Jeong Ra, Leslie Litzky, Tatiana Akimova, Ulf H Beier, Wayne W Hancock, Steven M Albelda, Evgeniy B Eruslanov
Data from mouse tumor models suggest that tumor-associated monocyte/macrophage lineage cells (MMLCs) dampen antitumor immune responses. However, given the fundamental differences between mice and humans in tumor evolution, genetic heterogeneity, and immunity, the function of MMLCs might be different in human tumors, especially during early stages of disease. Here, we studied MMLCs in early-stage human lung tumors and found that they consist of a mixture of classical tissue monocytes and tumor-associated macrophages (TAMs)...
February 13, 2019: Science Translational Medicine
X Zhang, Z Yu
PURPOSE: Phosphoinositide-dependent kinase 1 (PDK1) is highly expressed in many solid tumors. And several studies have demonstrated that PDK1 has been an emerging and promising target for anti-cancer therapies. However, the role of PDK1 has not been studied so far in malignant pheochromocytoma (PCC). METHODS: In this study, immunohistochemical staining was performed to investigate the protein level of PDK1 in 63 PCC tissue samples, of which 49 were benign and 14 were malignant...
February 13, 2019: Clinical & Translational Oncology
Abdallah S R Mohamed, Blaine D Smith, Joshua B Smith, Parag Sevak, Jessica S Malek, Aasheesh Kanwar, Theodora Browne, G Brandon Gunn, Adam S Garden, Steven J Frank, William H Morrison, Jack Phan, Mark Zafereo, Heath Skinner, Stephen Y Lai, Katherine A Hutcheson, Jan S Lewin, Amy E Hessel, Apurva A Thekdi, Randal S Weber, Clifton D Fuller, David I Rosenthal
OBJECTIVES: We aim to report oncologic outcomes after conventional radiotherapy (ConRT) using opposed lateral beams and intensity-modulated radiation therapy (IMRT) for tumor (T)1 nodal (N)0 T1 N0 glottic squamous cell carcinoma. STUDY DESIGN: Retrospective case-control study. METHODS: We retrospectively reviewed demographic, disease, and treatment characteristics for patients treated at our institution during 2000 to 2013. RESULTS: One hundred fifty-three patients (71%) were treated using ConRT and 62 (29%) using IMRT...
February 12, 2019: Laryngoscope
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