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Radioimmunotherapy

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https://www.readbyqxmd.com/read/28530668/radioimmunotherapy-augmented-beam-chemotherapy-vs-beam-alone-as-the-high-dose-regimen-for-autologous-stem-cell-transplantation-asct-in-relapsed-follicular-lymphoma-fl-a-retrospective-study-of-the-ebmt-lymphoma-working-party
#1
L Bento, A Boumendil, H Finel, S Le Gouill, S Amorim, H Monjanel, R Bouabdallah, J O Bay, E Nicolas-Virelizier, G McQuaker, G Rossi, R Johnson, A Huynh, P Ceballos, A Rambaldi, E Bachy, R Malladi, K Orchard, D Pohlreich, H Tilly, F Bonifazi, X Poiré, F Guilhot, A Haenel, C Crawley, B Metzner, J Gribben, N H Russell, G Damaj, K Thomson, P Dreger, S Montoto
Relapse remains the most common cause of treatment failure in patients receiving autologous stem cell transplantation (ASCT) for follicular lymphoma (FL). The aim of this study was to evaluate the effect of adding radioimmunotherapy or rituximab (R) to BEAM (carmustine, etoposide, ara-c, melphalan) high-dose therapy for ASCT in patients with relapsed FL. Using the European Society for Blood and Marrow Transplantation registry, we conducted a cohort comparison of BEAM (n=1973), Zevalin-BEAM (Z-BEAM) (n=207) and R-BEAM (n=179) and also a matched-cohort analysis of BEAM vs Z-BEAM including 282 and 154 patients, respectively...
May 22, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28521478/enhancement-of-antitumor-immunity-by-combination-of-anti-ctla-4-antibody-and-radioimmunotherapy-through-the-suppression-of-tregs
#2
Cheol-Hun Son, Jaeho Bae, Hong-Rae Lee, Kwangmo Yang, You-Soo Park
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of differentiation (CD)4+ T-cell activation and terminates immune responses by interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be constitutively expressed in regulatory T-cells (Tregs) and to contribute to immune suppression by enhancing the suppressive function of Tregs. However, the molecular mechanisms underlying CTLA-4-mediated Treg suppression remains incompletely understood. Furthermore, it is uncertain whether the in vivo immune suppressive functions of CTLA-4 are mediated only by a reduction in the level of conventional T-cell activity, or enhancement of Treg function...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28514062/locoregional-therapy-with-%C3%AE-emitting-trastuzumab-against-peritoneal-metastasis-of-her2-positive-gastric-cancer-in-mice
#3
Huizi Keiko Li, Yukie Morokoshi, Kotaro Nagatsu, Tadashi Kamada, Sumitaka Hasegawa
Peritoneal metastasis of gastric cancer (PMGC) is incurable and thus has an extremely poor prognosis. We have found however that locoregionally administered trastuzumab armed with a radionuclide astatine-211 ((211) At)-emitting α-particle ((211) At-trastuzumab) is effective against HER2-positive PMGC in a xenograft mouse model. We first observed that (211) At-trastuzumab can specifically bind and effectively kill NCI-N87 (N87) cells, which are HER2-positive human metastatic GC cells, both in vitro and in subcutaneous tumors...
May 17, 2017: Cancer Science
https://www.readbyqxmd.com/read/28504666/conditioning-regimens-for-allogeneic-hematopoietic-stem-cell-transplants-in-acute-myeloid-leukemia
#4
REVIEW
Y S Jethava, S Sica, B Savani, F Socola, M Jagasia, M Mohty, A Nagler, A Bacigalupo
AML is currently the first indication for allogeneic hematopoietic stem cell transplantation (allo-HSCT), as shown by international transplant registries. The conditioning regimens are classified as myeloablative conditioning, non-myeloablative or reduced intensity conditioning. Targeted radioimmunotherapy such as anti-CD45 antibody have also been added to the conditioning regimen in an attempt to improve tumor cell kill. Refinement of standard regimens has led to a reduction of non-relapse mortality, also in the older age group over 60 or 70 years of age...
May 15, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28498337/imaging-of-early-response-to-predict-prognosis-in-the-first-line-management-of-follicular-non-hodgkin-lymphoma-with-iodine-131-rituximab-radioimmunotherapy
#5
Murali Kesavan, Jan Boucek, William MacDonald, Andrew McQuillan, J Harvey Turner
The purpose of this study was to evaluate prediction of prognosis after first-line radioimmunotherapy (RIT) of advanced follicular non-Hodgkin lymphoma (FL), by imaging with fluorine-18-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) three months after induction treatment by Iodine-131-rituximab ((131)I-rituximab). Objective response was determined using the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline (18)F-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume (TMTV)...
May 12, 2017: Diagnostics
https://www.readbyqxmd.com/read/28491264/priming-radioimmunotherapy-with-external-beam-radiation-in-patients-with-relapsed-low-grade-non-hodgkin-lymphoma
#6
Yazan Abuodeh, Kamran Ahmed, Michelle Echevarria, Arash Naghavi, G Daniel Grass, Timothy J Robinson, Michael Tomblyn, Bijal Shah, Julio Chavez, Celeste Bello, Ghassan El-Haddad, Louis Harrison, Sungjune Kim
BACKGROUND: The aim of this study was to evaluate the outcomes of priming salvage radioimmunotherapy (RIT) with a low dose of external beam radiotherapy (EBRT) in patients with relapsed low grade non-Hodgkin lymphoma (LG-NHL). METHODS: Patients who received salvage RIT with or without 2 × 2 Gy EBRT between March 2009 and February 2013 were retrospectively reviewed at a single institution. Planning target volume (PTV) for EBRT was created by adding a 1-2 cm expansion to the gross tumor volume depending on the anatomical location...
April 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28466487/risk-of-histological-transformation-and-therapy-related-myelodysplasia-acute-myeloid-leukaemia-in-patients-receiving-radioimmunotherapy-for-follicular-lymphoma
#7
Narendranath Epperla, Anthony Q Pham, Brian L Burnette, Gregory A Wiseman, Thomas M Habermann, William R Macon, Stephen M Ansell, David J Inwards, Ivana N Micallef, Patrick B Johnston, Svetomir N Markovic, Luis F Porrata, Joseph P Colgan, Kay M Ristow, Grzegorz S Nowakowski, Thomas E Witzig
Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT...
May 3, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439844/therapeutic-efficacy-of-%C3%AE-radioimmunotherapy-with-different-activity-levels-of-the-213-bi-labeled-monoclonal-antibody-mx35-in-an-ovarian-cancer-model
#8
Anna Gustafsson-Lutz, Tom Bäck, Emma Aneheim, Ragnar Hultborn, Stig Palm, Lars Jacobsson, Alfred Morgenstern, Frank Bruchertseifer, Per Albertsson, Sture Lindegren
BACKGROUND: The aim of this study was to compare the therapeutic efficacy of two different activity levels of the (213)Bi-labeled monoclonal antibody MX35 in an ovarian cancer model. Sixty female BALB/c (nu/nu) mice were inoculated intraperitoneally with human ovarian cancer cells (OVCAR-3). Two weeks later, 40 mice were injected intraperitoneal (i.p.) with 1 ml of (213)Bi-MX35, 3 MBq/mL (n = 20), or 9 MBq/mL (n = 20). An additional 20 mice received unlabeled MX35. Incidence of tumors and ascites was investigated 8 weeks after therapy...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28430648/radioimmunotherapy-for-cd133-colonic-cancer-stem-cells-inhibits-tumor-development-in-nude-mice
#9
Dinghu Weng, Xueyan Jin, Saimei Qin, Xiaoli Lan, Chong Chen, Xun Sun, Xianliang She, Changling Dong, Rui An
Accumulating evidence indicates that cancer stem cells (CSCs) are the cause of tumor drug/radio-resistance or distant metastasis; therefore, it is essential to eliminate CSCs to cure cancer completely. The purpose of this study was to utilize radioimmunotherapy (RIT) to target CD133(+) colonic CSCs and observe whether this prevented tumor development, by assessing the maximum tolerated dose (MTD) of HCT116 tumor-bearing nude mice with escalating doses of 131I-AC133.1 monoclonal antibody (mAb), and determining the therapeutic efficacy of RIT with 131I-AC133...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428282/whither-radioimmunotherapy-to-be-or-not-to-be
#10
Damian J Green, Oliver W Press
Therapy of cancer with radiolabeled monoclonal antibodies has produced impressive results in preclinical experiments and in clinical trials conducted in radiosensitive malignancies, particularly B-cell lymphomas. Two "first-generation," directly radiolabeled anti-CD20 antibodies, (131)iodine-tositumomab and (90)yttrium-ibritumomab tiuxetan, were FDA-approved more than a decade ago but have been little utilized because of a variety of medical, financial, and logistic obstacles. Newer technologies employing multistep "pretargeting" methods, particularly those utilizing bispecific antibodies, have greatly enhanced the therapeutic efficacy of radioimmunotherapy and diminished its toxicities...
May 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28423546/tetraspanin-8-tspan-8-as-a-potential-target-for-radio-immunotherapy-of-colorectal-cancer
#11
Aurelie Maisonial-Besset, Tiffany Witkowski, Isabelle Navarro-Teulon, Odile Berthier-Vergnes, Giovanna Fois, Yingying Zhu, Sophie Besse, Olivia Bawa, Arnaud Briat, Mercedes Quintana, Alexandre Pichard, Mathilde Bonnet, Eric Rubinstein, Jean-Pierre Pouget, Paule Opolon, Lydia Maigne, Elisabeth Miot-Noirault, Jean-Michel Chezal, Claude Boucheix, Françoise Degoul
Tetraspanin 8 (TSPAN8) overexpression is correlated with poor prognosis in human colorectal cancer (CRC). A murine mAb Ts29.2 specific for human TSPAN8 provided significant efficiency for immunotherapy in CRC pre-clinical models. We therefore evaluate the feasability of targeting TSPAN8 in CRC with radiolabeled Ts29.2. Staining of tissue micro-arrays with Ts29.2 revealed that TSPAN8 espression was restricted to a few human healthy tissues. DOTA-Ts29.2 was radiolabeled with 111In or 177Lu with radiochemical purities >95%, specific activity ranging from 300 to 600 MBq/mg, and radioimmunoreactive fractions >80%...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413681/phase-2-study-of-chop-r-14-followed-by-90-y-ibritumomab-tiuxetan-in-patients-with-previously-untreated-diffuse-large-b-cell-lymphoma
#12
Reem Karmali, Melissa L Larson, Jamile M Shammo, Stephanie A Gregory, Teresa O'Brien, Parameswaran Venugopal
The aim of this open-label, single-center, phase 2 study was to assess the efficacy and safety of dose-dense CHOP-R-14 followed by (90)Y-ibritumomab radioimmunotherapy (RIT) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). A total of 20 patients, the majority presenting with high-risk characteristics, were enrolled to receive dose-dense cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab every 14 days (CHOP-R-14), followed by (90)Y-ibritumomab tiuxetan consolidation...
April 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28381167/cytokine-evaluation-in-untreated-and-radioimmunotherapy-treated-tumors-in-an-immunocompetent-rat-model
#13
Erika Elgström, Tomas G Ohlsson, Sophie E Eriksson
The tumor microenvironment can act so as to stimulate or reject tumor cells. Among the determining factors are cytokines produced, for example, by infiltrating immune cells, tumor cells, and fibroblasts. External radiotherapy has been shown to be able to activate an immune response against tumor cells with cytokine signaling as an important part of the activation. The aim of this study was to evaluate the cytokines present in the tumor microenvironment and whether the cytokine profile changed during tumor regression induced by radioimmunotherapy with the beta emitter (177)Lu...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28362640/multi-isotope-spect-imaging-of-the-225-ac-decay-chain-feasibility-studies
#14
A K H Robertson, C F Ramogida, C Rodríguez-Rodríguez, Stephan Blinder, Peter Kunz, Vesna Sossi, Paul Schaffer
Effective use of the [Formula: see text] decay chain in targeted internal radioimmunotherapy requires the retention of both [Formula: see text] and progeny isotopes at the target site. Imaging-based pharmacokinetic tests of these pharmaceuticals must therefore separately yet simultaneously image multiple isotopes that may not be colocalized despite being part of the same decay chain. This work presents feasibility studies demonstrating the ability of a microSPECT/CT scanner equipped with a high energy collimator to simultaneously image two components of the [Formula: see text] decay chain: [Formula: see text] (218 keV) and [Formula: see text] (440 keV)...
March 31, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28301261/a-radiolabeled-fully-human-antibody-to-human-aspartyl-asparaginyl-%C3%AE-hydroxylase-is-a-promising-agent-for-imaging-and-therapy-of-metastatic-breast-cancer
#15
Ekaterina Revskaya, Zewei Jiang, Alfred Morgenstern, Frank Bruchertseifer, Muctarr Sesay, Susan Walker, Steven Fuller, Michael S Lebowitz, Claudia Gravekamp, Hossein A Ghanbari, Ekaterina Dadachova
There is a need for novel effective and safe therapies for metastatic breast cancer based on targeting tumor-specific molecular markers of cancer. Human aspartyl (asparaginyl) β-hydroxylase (HAAH) is a highly conserved enzyme that hydroxylates epidermal growth factor-like domains in transformation-associated proteins and is overexpressed in a variety of cancers, including breast cancer. A fully human monoclonal antibody (mAb) PAN-622 has been developed to HAAH. In this study, they describe the development of PAN-622 mAb as an agent for imaging and radioimmunotherapy of metastatic breast cancer...
March 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28299759/optimizing-the-benefit-of-cns-radiation-therapy-in-the-pediatric-population-part-2-novel-methods-of-radiation-delivery
#16
REVIEW
Lindsay S Rowe, Andra V Krauze, Holly Ning, Kevin A Camphausen, Aradhana Kaushal
Newer approaches in the field of radiation therapy have raised the bar in the treatment of central nervous system (CNS) malignancies, with recognized advances that have aimed to increase the therapeutic index by improving conformality of the radiation dose to the planned target volume. Beyond these advances, the continued evolution of more effective systems for delivery of radiation to the CNS may offer further benefit not only to adults but also to pediatric patients, a cohort of the population that may be more sensitive to the long-term effects of radiation...
March 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28260607/preclinical-evaluation-of-131-i-bevacizumab-a-prospective-agent-for-radioimmunotherapy-in-vegf-expressing-cancers
#17
Mythili Kameswaran, Haladhar Dev Sarma, Ashutosh Dash
This study focuses on preparation and evaluation of (131)I-bevacizumab by Iodogen method for targeting VEGF over-expressing cancers for therapy. (131)I-Bevacizumab exhibited radiochemical purity of 98.0±0.7%. In vitro stability of (131)I-Bevacizumab was retained at >85% in both saline and serum at 37°C upto 5 days post iodination. In vitro cell studies showed good immunoreactivity and uptake by VEGF expressing tumor cells. Uptake and retention of (131)I-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirmed its specificity to VEGF...
February 16, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28254528/candidate-immune-biomarkers-for-radioimmunotherapy
#18
REVIEW
Antonin Levy, Giulia Nigro, Philippe J Sansonetti, Eric Deutsch
Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations...
February 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28191976/preloading-with-unlabeled-ca19-9-targeted-human-monoclonal-antibody-leads-to-improved-pet-imaging-with-89-zr-5b1
#19
Jacob L Houghton, Dalya Abdel-Atti, Wolfgang W Scholz, Jason S Lewis
CA19.9 is one of the most commonly occurring and highest density antigens in >90% of pancreatic cancers, making it an excellent target for monoclonal antibody (mAb)-based imaging and therapy applications. Preloading of unlabeled antibodies to enhance targeting of a radiolabeled mAb has been previously described both for imaging and radioimmunotherapy studies for other targets. We investigated the effect of preloading with the unmodified anti-CA19.9 antibody 5B1 on the uptake and contrast of the PET tracer (89)Zr-5B1 in subcutaneous and orthotopic murine models of pancreatic cancer utilizing Capan-2 xenografts, known to both express CA19...
March 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28181275/preparation-of-clinical-scale-177-lu-rituximab-optimization-of-protocols-for-conjugation-radiolabeling-and-freeze-dried-kit-formulation
#20
Mohini Guleria, Tapas Das, Chandan Kumar, Jeyachitra Amirdhanayagam, Haladhar D Sarma, Sharmila Banerjee
Rituximab is a monoclonal chimeric antibody, which has been approved by the US Food and Drug Administration for immunotherapy of non-Hodgkin lymphoma. Bexxar and Zevalin are the two other approved radiolabeled antibodies for radioimmunotherapy of non-Hodgkin lymphoma; however, they are of murine origin that reduces their treatment efficacy. So as to circumvent this, efforts have been made to radiolabel Rituximab with various therapeutic radioisotopes. In the present study, an effort has been made to optimize the conjugation (bifunctional chelating agent and antibody) and radiolabeling procedures for the preparation of clinical-scale (177) Lu-labeled Rituximab...
May 15, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
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