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abscopal effect

Xuanwei Zhang, Gabriele Niedermann
PURPOSE: Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell-mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 and 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses combined with anti-programmed cell death 1 (PD1) antibody treatment...
February 3, 2018: International Journal of Radiation Oncology, Biology, Physics
William Sperduto, David M King, Yoichi Watanabe, Emil Lou, Paul W Sperduto
Long-term survival for melanoma patients with multiple brain metastases is rare. A review of the literature reveals only three reported melanoma patients with multiple brain metastases who survived more than 10 years. We present a patient who is recurrence-free 11 years after the diagnosis of three brain metastases. Her treatment consisted of cytokine (interferon and interleukin-2) and chemotherapy nine months prior to developing brain and soft tissue metastases, which were treated with stereotactic radiosurgery and stereotactic ablative radiotherapy, respectively, followed by six months of chemotherapy...
December 14, 2017: Curēus
Jacob M Ricca, Anton Oseledchyk, Tyler Walther, Cailian Liu, Levi Mangarin, Taha Merghoub, Jedd D Wolchok, Dmitriy Zamarin
Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle Disease Virus (NDV) as a model, we explore the effects of pre-existing anti-viral immunity on therapeutic efficacy in syngeneic mouse tumor models. Unexpectedly, we find that while pre-existing immunity to NDV limits its replication in tumors, tumor clearance, abscopal anti-tumor immune effects, and survival are not compromised and, on the contrary, are superior in NDV-immunized mice...
January 31, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Silvia C Formenti, Percy Lee, Sylvia Adams, Judith D Goldberg, Xiaochun Li, Michael Xie, Josephine Ratikan, Carol Felix, Lin Hwang, Kym Faull, James W Sayre, Sara Hurvitz, John Glaspy, Begoña Comin-Anduix, Sandra Demaria, Dorthe Schaue, William H McBride
PURPOSE: This study examined the feasibility, efficacy (abscopal effect) and immune effects of TGFβ blockade during radiotherapy in metastatic breast cancer patients. EXPERIMENTAL DESIGN: Prospective randomized trial comparing two doses of TGFβ blocking antibody fresolimumab. Metastatic breast cancer patients with at least three distinct metastatic sites whose tumor had progressed after at least one line of therapy were randomized to receive 1 or 10 mg/kg of fresolimumab, every 3 weeks for 5 cycles, with focal radiotherapy to a metastatic site at week 1, (3 doses of 7...
February 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Zuzana Hlavata, Cinzia Solinas, Pushpamali De Silva, Michele Porcu, Luca Saba, Karen Willard-Gallo, Mario Scartozzi
Radiotherapy is one of the main treatment strategies used in cancer. Aside from the local control of the disease, which is mediated by a direct cytotoxic effect on tumor cells, radiotherapy has also been shown to exert immune-mediated local and systemic effects. Radiotherapy can elicit anti-tumor responses in distant sites from the radiation field; this phenomenon is known as the abscopal effect and has been described in patients previously treated with immune checkpoint blockade (ICB). Considering that the efficacy of immunotherapy has been demonstrated only in a subset of patients-who often benefit with lasting responses-efforts are ongoing to potentiate its activity with the development of new combination strategies...
February 22, 2018: Targeted Oncology
Wilfred Ngwa, Omoruyi Credit Irabor, Jonathan D Schoenfeld, Jürgen Hesser, Sandra Demaria, Silvia C Formenti
More than 60 years ago, the effect whereby radiotherapy at one site may lead to regression of metastatic cancer at distant sites that are not irradiated was described and called the abscopal effect (from 'ab scopus', that is, away from the target). The abscopal effect has been connected to mechanisms involving the immune system. However, the effect is rare because at the time of treatment, established immune-tolerance mechanisms may hamper the development of sufficiently robust abscopal responses. Today, the growing consensus is that combining radiotherapy with immunotherapy provides an opportunity to boost abscopal response rates, extending the use of radiotherapy to treatment of both local and metastatic disease...
February 16, 2018: Nature Reviews. Cancer
C Pleyers, P Piret, A Rorive, P A Coucke
Radiotherapy is known for its action on local tumoral control. However, it is also able to induce immunomodulatory effects at a systemic level. The abscopal effect (from latin ab scopus which means «away from the target») is an illustration of this phenomenon. It is defined as a tumor regression observed outside and at a distance of the irradiation fields. The potential application of this effect of treatment in disseminated cancers is a fast-growing field of research. The optimal therapeutic strategy to achieve this effect remains unknown...
January 2018: Revue Médicale de Liège
Thomas Walle, Rafael Martinez Monge, Adelheid Cerwenka, Daniel Ajona, Ignacio Melero, Fernando Lecanda
Radiotherapy (RT) is currently used in more than 50% of cancer patients during the course of their disease in the curative, adjuvant or palliative setting. RT achieves good local control of tumor growth, conferring DNA damage and impacting tumor vasculature and the immune system. Formerly regarded as a merely immunosuppressive treatment, pre- and clinical observations indicate that the therapeutic effect of RT is partially immune mediated. In some instances, RT synergizes with immunotherapy (IT), through different mechanisms promoting an effective antitumor immune response...
2018: Therapeutic Advances in Medical Oncology
Jean-Pierre Pouget, Alexandros G Georgakilas, Jean-Luc Ravanat
Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called "target" theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death...
January 19, 2018: Antioxidants & Redox Signaling
Lucas Basler, Aleksandra Kowalczyk, Regina Heidenreich, Mariola Fotin-Mleczek, Savas Tsitsekidis, Daniel Zips, Franziska Eckert, Stephan M Huber
BACKGROUND: Tumor metastasis and immune evasion present major challenges of cancer treatment. Radiotherapy can overcome immunosuppressive tumor microenvironments. Anecdotal reports suggest abscopal anti-tumor immune responses. This study assesses abscopal effects of radiotherapy in combination with mRNA-based cancer vaccination (RNActive®). METHODS: C57BL/6 mice were injected with ovalbumin-expressing thymoma cells into the right hind leg (primary tumor) and left flank (secondary tumor) with a delay of 4 days...
January 16, 2018: Cancer Immunology, Immunotherapy: CII
Moss Bruton Joe, Julian J Lum, Peter H Watson, R Petter Tonseth, John Paul McGhie, Pauline T Truong
The abscopal effect is a rare phenomenon in the setting of radiation therapy (RT) for metastatic cancer where tumor regression occurs distant from the site of treatment. A proposed mechanism of the abscopal effect is the activation of a systemic antitumor immune response by localized RT. We report the first case, to our knowledge, of the abscopal effect in squamous carcinoma of the anal canal with metastases to pelvic lymph nodes, liver and bone. After palliative RT to the pelvis with sensitizing chemotherapy, complete response was observed not only in the primary tumor but also in bone and multiple liver metastases at 4 months after treatment, an effect that remained durable at 4-year follow-up...
December 2017: Journal of Gastrointestinal Oncology
Jennifer R Hamilton, Gayathri Vijayakumar, Peter Palese
Influenza A virus (IAV) has shown promise as an oncolytic agent. To improve IAV as an oncolytic virus, we sought to design a transgenic virus expressing an immune checkpoint-inhibiting antibody during the viral life cycle. To test whether it was possible to express an antibody during infection, an influenza virus was constructed encoding the heavy chain of an antibody on the PB1 segment and the light chain of an antibody on the PA segment. This antibody-expressing IAV grows to high titers, and the antibodies secreted from infected cells exhibit comparable functionality with hybridoma-produced antibodies...
January 2, 2018: Cell Reports
Filipe Martins, Grégoire Stalder, Michel Obeid
No abstract text is available yet for this article.
December 26, 2017: Neoplasia: An International Journal for Oncology Research
Henry Wc Leung, Shyh-Yau Wang, Huang Jin-Jhih, Agnes Lf Chan
The abscopal effect is defined as the clearance of distant tumors after applying localized irradiation to a particular tumor site. It has been proposed that a mechanism for the abscopal effect might be the activation of the immune system, which leads to immunogenic tumor cell death. Here, we describe a woman with advanced breast cancer that received modified ablative radiation therapy that targeted her primary breast tumor. She experienced an apparent regression of metastatic mass in the thoracic spine. This case supported the hypothesis that the abscopal effect might be attributable to an activation of the systemic immune response...
December 27, 2017: Cancer Biology & Therapy
Silvia C Formenti
No abstract text is available yet for this article.
November 1, 2017: International Journal of Radiation Oncology, Biology, Physics
Ming-Cheng Chang, Yu-Li Chen, Han-Wei Lin, Ying-Cheng Chiang, Chi-Fang Chang, Shu-Feng Hsieh, Chi-An Chen, Wei-Zen Sun, Wen-Fang Cheng
Ionizing radiation therapy is a well-established method of eradicating locally advanced tumors. Here, we examined whether local RT enhanced the potency of an antigen-specific DNA vaccine, and we investigated the possible underlying mechanism. Using the HPV16 E6/E7+ syngeneic TC-1 tumor, we evaluated the combination of CTGF/E7 vaccination with local irradiation with regard to synergistic antigen-specific immunity and anti-tumor effects. Tumor-bearing mice treated with local RT (6 Gy twice weekly) and CTGF/E7 DNA vaccination exhibited dramatically increased numbers of E7-specific CD8+ cytotoxic T cell precursors, higher titers of anti-E7 Abs, and significantly reduced tumor size...
November 21, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
B Melichar, M Spisarová
The advent of immunotherapy has changed our concept of how to manage metastatic disease. With the exception of relatively rare tumors, the treatment of metastatic cancer is still considered as palliative, and in systemic treatment immunotherapy is often selected, considering better tolerance. Immunotherapy opens the perspective of a long-term, possibly durable, response, and, in contrast to other approaches to targeted therapy, is active across a spectrum of tumors. Combined regimens that increase the efficacy, given the context, are thus of importance...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Michael P Gustafson, Svetlana Bornschlegl, Sean S Park, Dennis A Gastineau, Lewis R Roberts, Allan B Dietz, Christopher L Hallemeier
Stereotactic body radiation therapy (SBRT) can positively influence an antitumor immune response by inducing necrotic cell death. SBRT also been shown to eliminate tumors outside the radiation therapy field through an immune-mediated process known as the abscopal effect. Recent advances in immunotherapy may provide new therapeutic approaches for patients with liver cancer. Therefore, understanding the immune status of patients with cancer will likely guide how immunotherapy might be used in combination with SBRT...
October 2017: Advances in Radiation Oncology
P Jack Hoopes, Courtney M Mazur, Bjorn Osterberg, Ailin Song, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Steven N Fiering
Although there is long association of medical hyperthermia and immune stimulation, the relative lack of a quantifiable and reproducible effect has limited the utility and advancement of this relationship in preclinical/clinical cancer and non-cancer settings. Recent cancer-based immune findings (immune checkpoint modulators etc.) including improved mechanistic understanding and biological tools now make it possible to modify and exploit the immune system to benefit conventional cancer treatments such as radiation and hyperthermia...
January 2017: Proceedings of SPIE
P Jack Hoopes, Karen L Moodie, Alicia A Petryk, James D Petryk, Shawntel Sechrist, David J Gladstone, Nicole F Steinmetz, Frank A Veliz, Alicea A Bursey, Robert J Wagner, Ashish Rajan, Danielle Dugat, Margaret Crary-Burney, Steven N Fiering
It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component...
January 2017: Proceedings of SPIE
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