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https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#1
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29774168/evaluating-the-potential-for-maximized-t-cell-redistribution-entropy-to-improve-abscopal-responses-to-radiotherapy
#2
Rachel Walker, Jonathan D Schoenfeld, Shari Pilon-Thomas, Jan Poleszczuk, Heiko Enderling
The potential for local radiation therapy to elicit systemic (abscopal) anti-tumor immune responses has been receiving a significant amount of attention over the last decade. We recently developed a mathematical framework designed to simulate the systemic dissemination of activated T cells among multiple metastatic sites. This framework allowed the identification of non-intuitive patterns of T cell redistribution after localized therapy, and offered suggestions as to the optimal site to irradiate in order to increase the magnitude of an immune-mediated abscopal response...
September 2017: Convergent Science Physical Oncology
https://www.readbyqxmd.com/read/29764160/combinatorial-strategies-of-radiotherapy-and-immunotherapy-in-nasopharyngeal-carcinoma
#3
Eugenia L L Yeo, You Quan Li, Khee-Chee Soo, Joseph T S Wee, Melvin L K Chua
Immunotherapy and radiation therapy (RT) have each demonstrated clinical success in the treatment of nasopharyngeal carcinoma (NPC) when utilized independently. Several characteristics of NPC make it particularly well suited for immunotherapeutic strategies, such as the association with viral infections like EBV and human papilloma virus (HPV), upregulation of PD-L1 expression, and the high number of tumor infiltrating lymphocytes. Immune checkpoint blockade is one such immunotherapeutic strategy that is gaining popularity rapidly...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29719740/abscopal-effect-in-a-stage-iv-melanoma-patient-who-progressed-on-pembrolizumab
#4
James M Tsui, Catalin Mihalcioiu, Fabio L Cury
In this case report, we present the clinical course of a woman with locally advanced mucosal melanoma of the oral cavity. She was initially treated with surgery with adjuvant local radiation of 50 Gy in 20 fractions. She quickly relapsed with an aggressive regional recurrence of the disease on the neck and with numerous pulmonary metastases. Immunotherapy with pembrolizumab was started, with initial good response and reduction in the size of the lesion in the neck. The regression, however, was short-lived, as the mass quickly grew at a remarkable rate and the lung lesions progressed significantly...
February 27, 2018: Curēus
https://www.readbyqxmd.com/read/29719632/molecular-mechanism-of-bystander-effects-and-related-abscopal-cohort-effects-in-cancer-therapy
#5
REVIEW
Rong Wang, Tingyang Zhou, Wei Liu, Li Zuo
Cancer cells subjected to ionizing radiation may release signals which can influence nearby non-irradiated cells, termed bystander effects. The transmission of bystander effects among cancer cells involves the activation of inflammatory cytokines, death ligands, and reactive oxygen/nitrogen species. In addition to bystander effects, two other forms of non-target effects (NTEs) have been identified in radiotherapy, as one is called cohort effects and the other is called abscopal effects. Cohort effects represent the phenomenon where irradiated cells can produce signals that reduce the survival of neighboring cells within an irradiated volume...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29699566/novel-oncolytic-chimeric-orthopoxvirus-causes-regression-of-pancreatic-cancer-xenografts-and-exhibits-abscopal-effect-at-a-single-low-dose
#6
Michael P O'Leary, Audrey H Choi, Sang-In Kim, Shyambabu Chaurasiya, Jianming Lu, Anthony K Park, Yanghee Woo, Susanne G Warner, Yuman Fong, Nanhai G Chen
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has been increasing by 0.5% per year in the United States. PDAC portends a dismal prognosis and novel therapies are needed. This study describes the generation and characterization of a novel oncolytic chimeric orthopoxvirus for the treatment of pancreatic cancer. METHODS: After chimerization and high-throughput screening, CF33 was chosen from 100 new chimeric orthopoxvirus isolates for its ability to kill pancreatic cancer cells...
April 26, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29680230/percutaneous-ablative-cryoimmunotherapy-for-micrometastaic-abscopal-effect-no-complications
#7
Erik Soule, Mark Bandyk, Jerry Matteo
Recent studies have shown efficacy of nivolumab, a monoclonal antibody specific for an immunoregulatory protein termed programmed death 1 (PD-1), against metastatic renal cell carcinoma. PD-1 is a transmembrane protein expressed on T cells that suppresses activation upon binding to its ligands, which may be secreted paraneoplastically by various cancers. Inhibition of PD-1 signaling via nivolumab may sensitize tumor-specific T lymphocytes in the immunosuppressive tumor microenvironment. Systemic elimination of micrometastases requires robust activation and proliferation of tumor antigen stimulated T cells...
April 19, 2018: Cryobiology
https://www.readbyqxmd.com/read/29666026/cervical-cancer-state-of-the-science-from-angiogenesis-blockade-to-checkpoint-inhibition
#8
REVIEW
Lindsey E Minion, Krishnansu S Tewari
Vascular endothelial growth factor (VEGF) has emerged as a therapeutic target in several malignancies, including cervical cancer. Chemotherapy doublets combined with the fully humanized monoclonal antibody, bevacizumab, now constitute first-line therapy for women struggling with recurrent/metastatic cervical carcinoma. Regulatory approval for this indication was based on the phase III randomized trial, GOG 240, which demonstrated a statistically significant and clinically meaningful improvement in overall survival when bevacizumab was added to chemotherapy: 17...
March 2018: Gynecologic Oncology
https://www.readbyqxmd.com/read/29665677/a-nanoscale-metal-organic-framework-overcomes-hypoxia-for-photodynamic-therapy-primed-cancer-immunotherapy
#9
Guangxu Lan, Kaiyuan Ni, Ziwan Xu, Samuel S Veroneau, Yang Song, Wenbin Lin
Immunotherapy has become a promising cancer therapy, but only works for a subset of cancer patients. Immunogenic photodynamic therapy (PDT) can prime cancer immunotherapy to increase the response rates, but its efficacy is severely limited by tumor hypoxia. Here we report a nanoscale metal-organic framework, Fe-TBP, as a novel nanophotosensitizer to overcome tumor hypoxia and sensitize effective PDT, priming non-inflamed tumors for cancer immunotherapy. Fe-TBP was built from iron clusters and porphyrin ligands and sensitized PDT under both normoxic and hypoxic conditions...
April 18, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29644338/hypothesis-can-the-abscopal-effect-explain-the-impact-of-adjuvant-radiotherapy-on-breast-cancer-mortality
#10
REVIEW
Ismail Jatoi, John R Benson, Ian Kunkler
Radiotherapy is an integral component of loco-regional therapy for breast cancer. Randomized controlled trials indicate that increasing the extent of extirpative surgery primarily reduces the risk of local recurrences, while the addition of radiotherapy to surgery can also reduce the risk of distant recurrences, thereby lowering breast cancer-specific mortality. This may suggest an "abscopal" effect beyond the immediate zone of loco-regional irradiation that favorably perturbs the natural history of distant micrometastases...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29644213/immunotherapy-plus-cryotherapy-potential-augmented-abscopal-effect-for-advanced-cancers
#11
REVIEW
Joe Abdo, David L Cornell, Sumeet K Mittal, Devendra K Agrawal
Since the 1920s the gold standard for treating cancer has been surgery, which is typically preceded or followed with chemotherapy and/or radiation, a process that perhaps contributes to the destruction of a patient's immune defense system. Cryosurgery ablation of a solid tumor is mechanistically similar to a vaccination where hundreds of unique antigens from a heterogeneous population of tumor cells derived from the invading cancer are released. However, releasing tumor-derived self-antigens into circulation may not be sufficient enough to overcome the checkpoint escape mechanisms some cancers have evolved to avoid immune responses...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29613803/treatment-of-canine-oral-melanoma-with-nanotechnology-based-immunotherapy-and-radiation
#12
P Jack Hoopes, Robert J Wagner, Kayla Duval, Kevin Kang, David J Gladstone, Karen L Moodie, Margaret Crary-Burney, Hugo Ariaspulido, Frank A Veliz, Nicole F Steinmetz, Steven Fiering
The presence and benefit of a radiation therapy-associated immune reaction is of great interest as the overall interest in cancer immunotherapy expands. Radiation therapy (RT) pathology studies have rarely demonstrated a consistent immune or inflammatory response following conventional RT. More recent information, primarily associated with the "abscopal effect", suggests a subtle radiation-based systemic immune response may be more common and have more therapeutic potential than previously believed...
April 3, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29601471/nanopulse-stimulation-nps-induces-tumor-ablation-and-immunity-in-orthotopic-4t1-mouse-breast-cancer-a-review
#13
REVIEW
Stephen J Beebe, Brittany P Lassiter, Siqi Guo
Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD)...
March 30, 2018: Cancers
https://www.readbyqxmd.com/read/29594244/combining-radiotherapy-and-ipilimumab-induces-clinically-relevant-radiation-induced-abscopal-effects-in-metastatic-melanoma-patients-a-systematic-review
#14
REVIEW
Rodolfo Chicas-Sett, Ignacio Morales-Orue, Delvys Rodriguez-Abreu, Pedro Lara-Jimenez
Background: In the last years, limited studies have described that radiotherapy could produce important distant responses in unirradiated sites, the so-called "abscopal effect". Recent evidence suggests that radiotherapy induces antigen release from tumor, in this way activating the immune system. However, radiotherapy alone is rarely enough to induce the systemic response requested for control of the metastases. With the advent of immunotherapy, the immune checkpoint inhibitors (ICI) have demonstrated impressive efficacy in various metastatic cancers...
February 2018: Clinical and Translational Radiation Oncology
https://www.readbyqxmd.com/read/29594038/priming-the-abscopal-effect-using-multifunctional-smart-radiotherapy-biomaterials-loaded-with-immunoadjuvants
#15
Michele Moreau, Sayeda Yasmin-Karim, Sijumon Kunjachan, Neeharika Sinha, Felix Gremse, Rajiv Kumar, Kwok Fan Chow, Wilfred Ngwa
In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated both on the right and left flank of each mouse, with the left tumor representing metastasis. The mice were randomized and divided into eight cohorts with four cohorts receiving image-guided RT (IGRT) at 5 Gy and another similar four cohorts at 0 Gy...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29592896/harnessing-and-optimizing-the-interplay-between-immunotherapy-and-radiotherapy-to-improve-survival-outcomes
#16
Kalpana Mujoo, Clayton R Hunt, Raj K Pandita, Mauro Ferrari, Sunil Krishnan, John P Cooke, Stephen Hahn, Tej K Pandita
In the past, radiation therapy was primarily used to control local disease but recent technological advances in accurate, high-dose ionizing radiation (IR) delivery have not only increased local tumor control but in some cases reduced metastatic burden. These "off target" therapeutic effects of IR at non-irradiated tumor sites, also known as abscopal effects, are thought to be mediated by tumor antigen-primed T cells that travel to metastatic sites and promote tumor regression. Similarly, early indications reveal that IR in combination with immune checkpoint inhibitors, such as ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1), can provide superior therapeutic responses...
March 28, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29584588/amelioration-of-head-and-neck-radiation-induced-mucositis-and-distant-marrow-suppression-in-fanca-and-fancg-mice-by-intraoral-administration-of-gs-nitroxide-jp4-039
#17
John Willis, Michael W Epperly, Renee Fisher, Xichen Zhang, Donna Shields, Wen Hou, Hong Wang, Song Li, Peter Wipf, Kalindi Parmar, Eva Guinan, Justin Steinman, Joel S Greenberger
Squamous cell carcinomas of the head and neck are appearing with increased frequency in both marrow transplanted and non-transplanted Fanconi anemia (FA) patients. FA patients commonly display radiosensitivity of epithelial tissues, complicating effective radiotherapy. Fancd2-/- mice (C57BL/6J and 129/Sv background) demonstrate epithelial tissue sensitivity to single-fraction or fractionated irradiation to the head and neck and distant marrow suppression (abscopal effect), both ameliorated by intraoral administration of the mitochondrial-targeted antioxidant, GS-nitroxide, JP4-039...
March 27, 2018: Radiation Research
https://www.readbyqxmd.com/read/29575297/sonodynamic-therapy-assisted-immunotherapy-a-novel-modality-for-cancer-treatment
#18
Qianyu Zhang, Cuixia Bao, Xiaojun Cai, Longwei Jin, Lingling Sun, Yuehong Lang, Libo Li
Sonodynamic therapy (SDT), which is based on photodynamic therapy (PDT), is a new cancer treatment modality. Unlike PDT, which has poor tissue penetration, ultrasound can penetrate deeply into tissues and largely target tumor tissue to mediate the cytotoxicity of sonosensitizers. We hypothesize that, similar to PDT, SDT may perform effectively as a cancer vaccines. Thus, we developed a therapeutic strategy to explore whether SDT can eliminate primary tumors, inhibit metastases, and prevent tumor relapse. In this study, we found that HiPorfin (HPD)-induced SDT killed tumor cells, promoted calreticulin expression on the cell surface and elicited immune responses...
March 25, 2018: Cancer Science
https://www.readbyqxmd.com/read/29569979/an-abscopal-effect-may-augment-pd-1-inhibition-in-refractory-classical-hodgkin-lymphoma
#19
Joel C Wight, Eliza A Hawkes, Salvatore U Berlangieri, Richard Khor, Andrew P Grigg
No abstract text is available yet for this article.
March 23, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29569509/the-future-impacts-of-non-targeted-effects
#20
Scott Bright, Munira Kadhim
PURPOSE: Ionizing radiation was traditionally thought to exert its detrimental effects through interaction with sensitive cellular targets, nuclear DNA being of most importance. This theory has since merged with a more recently described radiation response called non-targeted effects (NTE). This review will briefly look at the various types of NTE and the potential implications they may have for radiobiology research and its applications. CONCLUSIONS: The most well-known NTE are genomic instability (GI) and bystander effects (BE)...
March 23, 2018: International Journal of Radiation Biology
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