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https://www.readbyqxmd.com/read/28931759/combination-immunotherapy-with-tlr-agonists-and-checkpoint-inhibitors-suppresses-head-and-neck-cancer
#1
Fumi Sato-Kaneko, Shiyin Yao, Alast Ahmadi, Shannon S Zhang, Tadashi Hosoya, Megan M Kaneda, Judith A Varner, Minya Pu, Karen S Messer, Cristiana Guiducci, Robert L Coffman, Kazutaka Kitaura, Takaji Matsutani, Ryuji Suzuki, Dennis A Carson, Tomoko Hayashi, Ezra Ew Cohen
Checkpoint inhibitors have demonstrated efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, the majority of patients do not benefit from these agents. To improve the efficacy of checkpoint inhibitors, intratumoral (i.t.) injection with innate immune activators, TLR7 and TLR9 agonists, were tested along with programmed death-1 receptor (PD-1) blockade. The combination therapy suppressed tumor growth at the primary injected and distant sites in human papillomavirus-negative (HPV-negative) SCC7 and MOC1, and HPV-positive MEER syngeneic mouse models...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28929083/emerging-therapies-for-stage-iii-non-small-cell-lung-cancer-stereotactic-body-radiation-therapy-and-immunotherapy
#2
REVIEW
Sameera S Kumar, Kristin A Higgins, Ronald C McGarry
The current standard of care for locally advanced non-small cell lung cancer (NSCLC) includes radiation, chemotherapy, and surgery in certain individualized cases. In unresectable NSCLC, chemoradiation has been the standard of care for the past three decades. Local and distant failure remains high in this group of patients, so dose escalation has been studied in both single institution and national clinical trials. Though initial studies showed a benefit to dose escalation, phase III studies examining dose escalation using standard fractionation or hyperfractionation have failed to show a benefit...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28920000/oncolytic-peptide-ltx-315-induces-an-immune-mediated-abscopal-effect-in-a-rat-sarcoma-model
#3
Janne Nestvold, Meng-Yu Wang, Ketil A Camilio, Severin Zinöcker, Torunn Elisabeth Tjelle, Alf Lindberg, Bengt Erik Haug, Gunnar Kvalheim, Baldur Sveinbjørnsson, Øystein Rekdal
LTX 315 is an oncolytic peptide with potent immunological properties. In the present study, we demonstrate that intratumoral treatment with LTX-315 resulted in a complete regression and systemic immune response in a rat fibrosarcoma model. The treatment was T-cell dependent, and also resulted in an abscopal effect as demonstrated by the regression of distal non-treated lesions. Significant infiltration of CD8(+) T cells was observed in both treated and non-treated lesions, as shown by immunohistochemical and flow cytometric analysis...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28905118/administration-of-low-dose-combination-anti-ctla4-anti-cd137-and-anti-ox40-into-murine-tumor-or-proximal-to-the-tumor-draining-lymph-node-induces-systemic-tumor-regression
#4
Jonathan P O Hebb, Adriane R Mosley, Felipe Vences-Catalán, Narendiran Rajasekaran, Anna Rosén, Peter Ellmark, Dean W Felsher
The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. The triple combination administered intratumorally at low doses to one tumor of a dual tumor mouse model had dramatic local and systemic anti-tumor efficacy in lymphoma (A20) and solid tumor (MC38) models, consistent with an abscopal effect...
September 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28872544/soft-tissue-response-on-18f-fluorocholine-pet-ct-in-metastatic-castrate-resistant-prostate-cancer-treated-with-223ra-dichloride-a-possible-abscopal-effect
#5
Sandi A Kwee, John Lim, Marc N Coel
Two patients with castrate-resistant prostate cancer and symptomatic skeletal metastases underwent F-fluorocholine PET/CT prior to treatment with Ra-dichloride to reveal additional active lesions in the prostate gland and lymph nodes. Subsequent scans performed at the midpoint and end of Ra-dichloride therapy showed resolution of this soft tissue activity alongside declining bone lesion activity. Concomitant increases in plasma interleukin 6 were detected, suggesting that immune system activation may have mediated the soft tissue response...
September 1, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28871985/stimulating-innate-immunity-to-enhance-radiation-therapy-induced-tumor-control
#6
REVIEW
Jason R Baird, Arta M Monjazeb, Omid Shah, Heather McGee, William J Murphy, Marka R Crittenden, Michael J Gough
Novel ligands that target Toll-like receptors and other innate recognition pathways represent a potent strategy for modulating innate immunity to generate antitumor immunity. Although many of the current clinically successful immunotherapies target adaptive T-cell responses, both preclinical and clinical studies suggest that adjuvants have the potential to enhance the scope and efficacy of cancer immunotherapy. Radiation may be a particularly good partner to combine with innate immune therapies, because it is a highly efficient means to kill cancer cells but may fail to send the appropriate inflammatory signals needed to act as an efficient endogenous vaccine...
October 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28870955/correlation-of-radiation-pneumonitis-history-before-nivolumab-with-onset-of-interstitial-lung-disease-and-progression-free-survival-of-patients-with-pre-treated-advanced-non-small-cell-lung-cancer
#7
Akihiro Tamiya, Motohiro Tamiya, Kenji Nakahama, Yoshihiko Taniguchi, Takayuki Shiroyama, Shun-Ichi Isa, Takako Inoue, Kyoichi Okishio, Kazumi Nishino, Toru Kumagai, Hidekazu Suzuki, Tomonori Hirashima, Fumio Imamura, Shinji Atagi
BACKGROUND/AIM: Nivolumab has a promising efficacy for patients with non-small-cell lung cancer (NSCLC) as second-line or later treatment, and after radiotherapy as abscopal effect. However, the effects of radiation pneumonitis history before nivolumab have not been clarified. Therefore, we retrospectively analyzed the correlation of a history of radiation pneumonitis before nivolumab with onset of interstitial lung disease (ILD) and progression-free survival (PFS) after nivolumab treatment in patients with previously treated NSCLC...
September 2017: Anticancer Research
https://www.readbyqxmd.com/read/28858075/concurrent-radiotherapy-for-patients-with-metastatic-melanoma-and-receiving-anti-programmed-death-1-therapy-a-safe-and-effective-combination
#8
Amélie Aboudaram, Anouchka Modesto, Léonor Chaltiel, Carlos Gomez-Roca, Serge Boulinguez, Vincent Sibaud, Jean-Pierre Delord, Ciprian Chira, Martine Delannes, Elizabeth Moyal, Nicolas Meyer
A combination of immune-checkpoint inhibitors and radiation therapy (RT) represents a promising therapeutic strategy in part mediated by the abscopal effect, but clinical experience related to this combination remains scarce. Clinical data and patterns of treatment were retrospectively collected from all consecutive patients with metastatic melanoma and receiving programmed-death 1 (PD-1) immune-checkpoint inhibitors. Survival data, best overall response, and acute and delayed toxicities (graded according to Common Terminology Criteria for Adverse Events, v 4...
October 2017: Melanoma Research
https://www.readbyqxmd.com/read/28838649/brachytherapy-attains-abscopal-effects-when-combined-with-immunostimulatory-monoclonal-antibodies
#9
María E Rodriguez-Ruiz, Inmaculada Rodriguez, Benigno Barbes, Lina Mayorga, Alfonso Rodriguez Sanchez-Paulete, Mariano Ponz-Sarvise, José Luis Pérez-Gracia, Ignacio Melero
PURPOSE/OBJECTIVES: Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory monoclonal antibodies (mAb) to act both on irradiated tumor lesions and on tumors at distant, nonirradiated sites. We have recently reported that external beam radiotherapy achieves abscopal effects when combined with antagonist anti-PD1 mAbs and agonist anti-CD137 (4-1BB) mAbs. The goal of this work is to study the abscopal effects of radiotherapy instigated by brachytherapy techniques...
August 21, 2017: Brachytherapy
https://www.readbyqxmd.com/read/28795608/focus-small-to-find-big-the-microbeam-story
#10
Jinhua Wu, Tom K Hei
PURPOSE: Even though the first ultraviolet microbeam was described by S. Tschachotin back in 1912, the development of sophisticated micro-irradiation facilities only began to flourish in the late 1980s. In this article, we highlight significant microbeam experiments, describe the latest microbeam irradiator configurations and critical discoveries made by using the microbeam apparatus. MATERIALS AND METHODS: Modern radiological microbeams facilities are capable of producing a beam size of a few micrometers, or even tens of nanometers in size, and can deposit radiation with high precision within a cellular target...
August 10, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28791476/abscopal-effect-of-boron-neutron-capture-therapy-bnct-proof-of-principle-in-an-experimental-model-of-colon-cancer
#11
Verónica A Trivillin, Emiliano C C Pozzi, Lucas L Colombo, Silvia I Thorp, Marcela A Garabalino, Andrea Monti Hughes, Sara J González, Rubén O Farías, Paula Curotto, Gustavo A Santa Cruz, Daniel G Carando, Amanda E Schwint
The aim of the present study was to evaluate, for the first time, the abscopal effect of boron neutron capture therapy (BNCT). Twenty-six BDIX rats were inoculated subcutaneously with 1 × 10(6) DHD/K12/TRb syngeneic colon cancer cells in the right hind flank. Three weeks post-inoculation, the right leg of 12 rats bearing the tumor nodule was treated with BPA-BNCT (BPA-Boronophenylalanine) at the RA-3 nuclear reactor located in Buenos Aires, Argentina, at an absorbed dose of 7.5 Gy to skin as the dose-limiting tissue...
August 8, 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28721900/triggering-the-abscopal-effect-is-the-quality-of-the-radiation-important
#12
Frederik J Vernimmen, Jill T Nicholson
No abstract text is available yet for this article.
August 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28686524/hunting-for-abscopal-and-bystander-effects-clinical-exploitation-of-non-targeted-effects-induced-by-partial-high-single-dose-irradiation-of-the-hypoxic-tumour-segment-in-oligometastatic-patients
#13
https://www.readbyqxmd.com/read/28680762/tumor-targeted-il-12-combined-with-local-irradiation-leads-to-systemic-tumor-control-via-abscopal-effects-in-vivo
#14
Franziska Eckert, Ivan Jelas, Moritz Oehme, Stephan M Huber, Katja Sonntag, Christian Welker, Stephen D Gillies, Wolfgang Strittmatter, Daniel Zips, Rupert Handgretinger, Karin Schilbach
NHS-IL12 is an immunocytokine, a fusion protein of IL12's functional domains and a necrosis-targeting antibody, which has shown significant effects against human rhabdomyosarcoma xenografts in a humanized tumor model, including terminal growth arrest and differentiation of the tumor cells. Here, we locally irradiated the tumors, increasing necrosis and consequently intratumoral immune cytokine availability, and asked whether this effect may surmount efficacy of single treatment modality. Humanized mice bearing bilateral rhabdomyosarcoma xenografts were evaluated for tumor burden and survival after irradiation, systemic NHS-IL12 therapy or a combination of both...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28677658/abscopal-activation-of-microglia-in-embryonic-fish-brain-following-targeted-irradiation-with-heavy-ion-microbeam
#15
Takako Yasuda, Miyuki Kamahori, Kento Nagata, Tomomi Watanabe-Asaka, Michiyo Suzuki, Tomoo Funayama, Hiroshi Mitani, Shoji Oda
Microglia remove apoptotic cells by phagocytosis when the central nervous system is injured in vertebrates. Ionizing irradiation (IR) induces apoptosis and microglial activation in embryonic midbrain of medaka (Oryzias latipes), where apolipoprotein E (ApoE) is upregulated in the later phase of activation of microglia In this study, we found that another microglial marker, l-plastin (lymphocyte cytosolic protein 1), was upregulated at the initial phase of the IR-induced phagocytosis when activated microglia changed their morphology and increased motility to migrate...
July 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28674082/intratumoral-sting-activation-with-t-cell-checkpoint-modulation-generates-systemic-antitumor-immunity
#16
Casey R Ager, Matthew J Reilley, Courtney Nicholas, Todd Bartkowiak, Ashvin R Jaiswal, Michael A Curran
Coordinated manipulation of independent immune regulatory pathways in the tumor microenvironment-including blockade of T-cell checkpoint receptors and reversal of suppressive myeloid programs-can render aggressive cancers susceptible to immune rejection. Elevated toxicity associated with combination immunotherapy, however, prevents translation of the most efficacious regimens. We evaluated T-cell checkpoint-modulating antibodies targeting CTLA-4, PD-1, and 4-1BB together with myeloid agonists targeting either STING or Flt3 in the TRAMP-C2 model of prostate cancer to determine whether low-dose intratumoral delivery of these agents could elicit systemic control of multifocal disease...
August 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28665741/a-rapid-and-systemic-complete-response-to-stereotactic-body-radiation-therapy-and-pembrolizumab-in-a-patient-with-metastatic-renal-cell-carcinoma
#17
Guozhu Xie, Di Gu, Lanfang Zhang, Shijun Chen, Dehua Wu
Stereotactic body radiation therapy (SBRT) of local tumor would induce an abscopal effect that has been observed in several kinds of human cancers; one important mechanism may involve the improved activation of the host immune system. The immune checkpoint inhibitor can overcome immune tolerance and enhance the activation of antitumor T cells. The combined treatment of SBRT and checkpoint inhibitor may represent a new promising therapeutic approach. Herein, we reported a patient with metastatic renal cell carcinoma (RCC) treated with concurrent SBRT and anti-PD-1 antibody, pembrolizumab, by which the patient achieved an amazingly systemic complete response in only 2...
June 30, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28650437/antigen-capturing-nanoparticles-improve-the-abscopal-effect-and-cancer-immunotherapy
#18
Yuanzeng Min, Kyle C Roche, Shaomin Tian, Michael J Eblan, Karen P McKinnon, Joseph M Caster, Shengjie Chai, Laura E Herring, Longzhen Zhang, Tian Zhang, Joseph M DeSimone, Joel E Tepper, Benjamin G Vincent, Jonathan S Serody, Andrew Z Wang
Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties...
September 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28621265/improving-radiotherapy-in-cancer-treatment-promises-and-challenges
#19
REVIEW
Helen H W Chen, Macus Tien Kuo
Effective radiotherapy for cancer has relied on the promise of maximally eradicating tumor cells while minimally killing normal cells. Technological advancement has provided state-of-the-art instrumentation that enables delivery of radiotherapy with great precision to tumor lesions with substantial reduced injury to normal tissues. Moreover, better understanding of radiobiology, particularly the mechanisms of radiation sensitivity and resistance in tumor lesions and toxicity in normal tissues, has improved the treatment efficacy of radiotherapy...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598415/dna-exonuclease-trex1-regulates-radiotherapy-induced-tumour-immunogenicity
#20
Claire Vanpouille-Box, Amandine Alard, Molykutty J Aryankalayil, Yasmeen Sarfraz, Julie M Diamond, Robert J Schneider, Giorgio Inghirami, C Norman Coleman, Silvia C Formenti, Sandra Demaria
Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12-18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Cytosolic DNA stimulates secretion of interferon-β by cancer cells following activation of the DNA sensor cGAS and its downstream effector STING...
June 9, 2017: Nature Communications
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