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A phase I radioimmunotherapy trial evaluating 90yttrium-labeled anti-carcinoembryonic antigen (CEA) chimeric T84.66 in patients with metastatic CEA-producing malignancies.

Chimeric T84.66 (cT84.66) is a genetically engineered human/murine chimeric IgG, with high affinity and specificity to carcinoembryonic anti … structs derived from cT84.66 continue to be evaluated in preclinical models as potential agents for radioimmunotherapy.

Imaging of Early Response to Predict Prognosis in the First-Line Management of Follicular Non-Hodgkin Lymphoma with Iodine-131-Rituximab Radioimmunotherapy.

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 (18F-FDG-PET/CT) three months after induction treatment by Iodine-131-rituximab (131I-rituximab). Objective response was determined using the Deauville 5-point scale in 68 prospective clinical trial patients. Baseline 18F-FDG-PET/CT studies were used to calculate total-metabolic-tumor-volume (TMTV). Non-imaging studies included the Follicu…

Radioimmunotherapy with Tenarad, a 131I-labelled antibody fragment targeting the extra-domain A1 of tenascin-C, in patients with refractory Hodgkin's lymphoma.

PURPOSE: The extra-domain A1 of tenascin-C (TC-A1) is highly expressed in the extracellular matrix of tumours and on newly formed blood vessels and is thus a valuable target for radionuclide therapy. Tenarad is a fully human miniantibody or small immunoprotein (SIP, molecular weight 80 kDa) labelled with (131)I that is derived from a TC-A1-binding antibody. Previous phase I/II studies with a similar compound ((131)I-L19SIP) used for radioimmunotherapy (RIT) have shown preliminary efficacy in a variety of cancer types. In this ongoing phase I/II trial, Tenarad was administered to patients with …

High rates of durable responses with anti-CD22 fractionated radioimmunotherapy: results of a multicenter, phase I/II study in non-Hodgkin's lymphoma.

PURPOSE: Fractionated radioimmunotherapy targeting CD22 may substantially improve responses and outcome in non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: A multicenter trial evaluated two or three weekly infusions of yttrium-90 ((90)Y) epratuzumab tetraxetan (humanized anti-CD22 antibody) in 64 patients with relapsed/refractory NHL, including 17 patients who underwent prior autologous stem-cell transplantation (ASCT). Objective (OR) and complete responses (CR/complete response unconfirmed [CRu]), as well as progression-free survival (PFS), were determined. RESULTS: At the maximum total …

Pretargeted Anti-CD20 Radioimmunotherapy with scFv Fusion Protein Safely Combines with BEAM and ASCT in Patients with High-risk B-cell Lymphomas.

Despite new therapies, many patients with non-Hodgkin lymphoma (NHL) relapse and need more effective salvage therapies. This study (NCT02483000) evaluated the safety of B9E9-FP, a tetrameric single-chain anti-CD20-streptavidin fusion protein used in pretargeted radioimmunotherapy, when combined with BEAM and autologous stem cell transplantation (ASCT) for patients with NHL. Patients with high-risk NHL received B9E9-FP on day -17, clearing agent on day -15, and DOTA-biotin (DOTA-Bt) equally divided and labeled with dose-escalated yttrium-90 (90Y) or with indium-111 (for imaging) on day -14. BEA…

Prediction of therapy tumor-absorbed dose estimates in I-131 radioimmunotherapy using tracer data via a mixed-model fit to time activity.

BACKGROUND: For individualized treatment planning in radioimmunotherapy (RIT), correlations must be established between tracer-predicted and therapy-delivered absorbed doses. The focus of this work was to investigate this correlation for tumors. METHODS: The study analyzed 57 tumors in 19 follicular lymphoma patients treated with I-131 tositumomab and imaged with SPECT/CT multiple times after tracer and therapy administrations. Instead of the typical least-squares fit to a single tumor's measured time-activity data, estimation was accomplished via a biexponential mixed model in which the curv…

Dose-attenuated radioimmunotherapy with tositumomab and iodine 131 tositumomab in patients with recurrent non-Hodgkin's lymphoma (NHL) and extensive bone marrow involvement.

Radioimmunotherapy (RIT) with tositumomab and iodine 131 tositumomab can produce durable and complete responses in relapsed/refractory low-grade Non-Hodgkin's lymphoma. Patients with bone marrow involvement (BMI) with tumor >25% of the intertrabecular space are generally excluded from RIT because of risk of excessive hematologic toxicity. The authors conducted a dose-escalation study of tositumomab and iodine 131 tositumomab to determine whether RIT is feasible in this population. Patients had baseline BMI of >25% and platelet count of >or=150,000/mm3. In contrast to the usual 75 cGy total bod…

A senescence-associated gene signature predicts radiotherapy prognosis in non-small cell lung cancer and identifies CSF1 as a target to potentiate radioimmunotherapy.

The role of cellular senescence as a tumor-associated hallmark and therapeutic target in influencing radiotherapy or radioimmunotherapy outcomes remains incompletely understood. To address this, we developed a senescence-associated gene signature to predict prognosis in non‑small cell lung cancer (NSCLC) patients treated with radiotherapy. A risk model based on nine genes-including COL4A1 and CSF1-effectively stratified patients into high‑ and low‑risk groups. High‑risk patients exhibited significantly poorer overall survival and a tumor microenvironment characterized by reduced immune infiltr…

Craniospinal irradiation and/or intraventricular radioimmunotherapy after high-dose chemotherapy and autologous stem cell rescue in patients with CNS retinoblastoma-Safety and outcomes.

BACKGROUND: The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated … front therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n = 3), intraventricular radioimmunotherapy (n = 3), or both CSI and intraventricular radioimmunotherapy (n = 1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5 years; no patients developed second malignant neoplasms within the radiation fields. For the seven …

Utility of 211At-Trastuzumab for the Treatment of Metastatic Gastric Cancer in the Liver: Evaluation of a Preclinical α-Radioimmunotherapy Approach in a Clinically Relevant Mouse Model.

A liver metastasis from a primary gastric cancer (LMGC) is relatively common and results in an extremely poor prognosis due to a lack of effective therapeutics. We here demonstrate in a clinically relevant mouse model that an α-particle radioimmunotherapy approach with 211At-labeled trastuzumab has efficacy against LMGCs that are positive for human epidermal growth factor receptor 2 (HER2). Methods:211At was produced in a cyclotron via a 209Bi (α,2n) 211At reaction. 211At-trastuzumab was subsequently generated using a single-step labeling method. NCI-N87 cells (HER2-positive human gastric canc…

Is there need for radioimmunotherapy? results of a phase I/II study in patients with indolent B-cell lymphomas using lutetium-177-DOTA-rituximab.

AIM: The aim of the study was to explore the clinical response to 177Lutetium-DOTA-rituximab (177Lu-D-R) and to determine the maximum tolerated dose (MTD) in the treatment of patients with relapsed follicular, mantle cell or other indolent lymphomas such as marginal zone lymphoma as well as to put these results into context with other therapy options for these patients. METHODS: Treatment consisted of cold rituximab (250 mg/m2) on day 1 and day 8 and 177Lu-DOTA-Rituximab on day 8. Reassessment was done at week 10. Thirty-one patients (males=17, females=14, median number of pretreatments: 3) w

The asymptomatic follicular lymphoma (AFL) trial: single-agent rituximab immunotherapy versus 90Y-ibritumomab tiuxetan radioimmunotherapy (RIT) for patients with new, untreated follicular lymphoma.

Patients with asymptomatic follicular lymphoma (AFL) are candidates for observation or immunotherapy. Given the effectiveness of radiation therapy in FL, another option is 90Yttrium-ibritumomab tiuxetan radioimmunotherapy (RIT). We conducted a trial where untreated AFL patients were randomized to rituximab 375 mg/m2 weekly × 4 or rituximab 250 mg/m2 days 1, 8, and 0.4 mCi/kg (maximum 32 mCi) of RIT day 8. Twenty patients were enrolled before the study was halted due to unavailability of RIT. The ORR for rituximab and RIT were 90% and 80%, respectively; the CR rate at 6 months was 30% and 60%, …

The role of 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma after radioimmunotherapy using 131I-rituximab as consolidation therapy.

PURPOSE: To evaluate the prognostic value of pretreatment 18F-FDG PET/CT after consolidation therapy of 131I-rituximab in patients with diffuse large B-cell lymphoma (DLBCL) who had acquired complete remission after receiving chemotherapy. METHODS: Patients who were diagnosed with DLBCL via histologic confirmation were retrospectively reviewed. All patients had achieved complete remission after 6 to 8 cycles of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) chemotherapy after which they underwent consolidation treatment with 131I-rituximab. 18F-FDG PET/CT sca

B7H3-Directed Intraperitoneal Radioimmunotherapy With Radioiodinated Omburtamab for Desmoplastic Small Round Cell Tumor and Other Peritoneal Tumors: Results of a Phase I Study.

PURPOSE: Desmoplastic small round cell tumor (DSRCT), a rare sarcoma of adolescents/young adults primarily involving the peritoneum, has a long-term survival of < 20% despite aggressive multimodality treatment. B7H3 is expressed on DSRCT cell surface, providing a target for antibody-based immunotherapy. PATIENTS AND METHODS: In this phase I study, we evaluated the safety, pharmacokinetics, and biodistribution of intraperitoneal (IP) radioimmunotherapy (RIT) with the anti-B7H3 murine monoclonal antibody 131I-omburtamab in patients with DSRCT or other B7H3-expressing tumors involving the perito…

Pre-treatment partial-volume-corrected TLG is the best predictor of overall survival in patients with relapsing/refractory non-hodgkin lymphoma following radioimmunotherapy.

The role of fluorodeoxyglucose-positron emission tomography (FDG-PET) has been well established in assessment of lymphoma, including non-Hodgkin lymphoma (NHL). The aim of this study was to compare changes and survival predictive values of various quantification parameters of FDG-PET/CT in patients with relapsing/refractory lymphoma before and after radioimmunotherapy (RIT). Data from 17 patients with relapsing/refractory NHL, treated with targeted RIT after chemotherapy/radiotherapy, were retrospectively collected. FDG-PET/CT scans were performed approximately three months before and six mont…

Collection of hematopoietic stem cells after previous radioimmunotherapy is feasible and does not impair engraftment after autologous stem cell transplantation in follicular lymphoma.

Major concerns about radioimmunotherapy (RIT) administration early in the course of follicular lymphoma (FL) are long-term toxicity and the theoretical impairment of hematopoietic stem cell (HSC) harvest, but few data are available about mobilization rates after RIT. This study evaluates the impact of prior therapy with RIT (yttrium-90 ibritumomab tiuxetan) and different chemotherapy regimens in all FL patients (N = 103) attempting HSC mobilization at our institution over the last 7 years. Sixty-nine patients received R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone) or CH…

Radioimmunotherapy of relapsed indolent non-Hodgkin lymphoma with 131I-rituximab in routine clinical practice: 10-year single-institution experience of 142 consecutive patients.

Radioimmunotherapy of indolent non-Hodgkin lymphoma (NHL) has achieved objective response rates in clinical trials comparable with standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, but is relatively underused in routine practice. In this article, we report our clinical experience in 142 consecutive patients who received iodine-131 rituximab radioimmunotherapy for low-grade, predominantly follicular, relapsed NHL. Objective response rates of 67%, with complete response (CR) in 50% and median overall survival of 32 months, matched the response rates…

Fingolimod синхронизирует с радиоиммунотерапией против PD-1 в экспериментальной множественной склерозовой модели путем усиления лимфатического узла и разрушения клеток CD8+T.

ВВЕДЕНИЕ: Множественный склероз (MS) является хроническим нейродегенеративным аутоиммунным заболеванием, вызванным ненадлежащим активированием иммунной системы, нацеленной на антигены центральной нервной системы, например миелин. Некоторые MS-терапии контролируют болезнь за счет истощения CD20+B клеток и поглощения T лимфоцитов в лимфоузлах. Оптимальным был бы целенаправленный подход, направленный на истощение только активированных Т лимфоцитов, которые играют ключевую роль в прогрессии заболеваний. Программный белок смерти клеток 1 (PD-1) — ингибиторный рецептор, выраженный на изнурённых и не

Совпадение в аннотации оригинала
INTRODUCTION: Multiple sclerosis (MS) is a chronic neurodegenerative autoimmune disease caused by inappropriate activation of the immune sys … ently activated T cells. We have previously reported success with [177Lu]Lu-anti-PD-1 (177Lu-αPD-1) radioimmunotherapy (RIT) as a standalone treatment in experimental autoimmune encephalomyelitis (EAE), which is the most common preclinical model of MS. In this study, we present the synergistic effect of fingolimod (FTY720/Gilenya™) in combination with [177Lu]Lu-αPD- …

Phase II study of first-line (131)I-rituximab radioimmunotherapy in follicular non-Hodgkin lymphoma and prognostic (18)F-fluorodeoxyglucose positron emission tomography.

First-line (131)I-anti-CD20 radioimmunotherapy of indolent non-Hodgkin lymphoma (NHL) achieves durable remission with low toxicity. The phase II INITIAL study comprised 68 patients with follicular NHL followed up to 7 years (median 4 years) after outpatient (131)I-rituximab radioimmunotherapy (RIT) in conjunction with rituximab, followed by maintenance therapy for 1 year. Baseline and 3-month (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) imaging, analyzed according to Deauville criteria, was used to evaluate response and predict prognosis. The overall response rate at 3…

Prospective trial of targeted radioimmunotherapy with Y-90 ibritumomab tiuxetan (Zevalin) for front-line treatment of early-stage extranodal indolent ocular adnexal lymphoma.

BACKGROUND: To determine the efficacy and side-effects of (90)Y ibritumomab tiuxetan (Zevalin) as front-line treatment in patients with early-stage extranodal indolent lymphoma of the ocular adnexa (orbit, conjunctiva, or eyelid). PATIENTS AND METHODS: From August 2004 to November 2007, 12 patients with stages I-E extranodal indolent lymphoma of the ocular adnexa were enrolled in a prospective trial of rituximab followed by (90)Y ibritumomab tiuxetan (Zevalin therapeutic regimen). For each patient, clinical examinations and imaging studies were used to document response to therapy using the T