Pretargeted radioimmunotherapy: clinically more efficient than conventional radioimmunotherapy?

Rousseau, Caroline; Kraeber-Bodéré, Françoise; Barbet, Jacques; Chatal, Jean‐François

doi:10.1007/s00259-013-2469-9

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…11 The group of Kraeber-Bode ´re ´intensively investigated this second generation pretargeting procedure regarding the treatment of CEAproducing medullary thyroid carcinoma (MTC) in several preclinical as well as clinical studies 10 and critically compared the toxicity and efficacy of pretargeted RIT with those of conventional RIT. 15 The first as well as second generation of bs mAbs-based pretargeting systems utilised anti-chelate antibodies with an exceptional specificity for a certain radiometal-chelate complex, e.g. 111 In-loaded DTPA.…”

Section: Recognition Systems Based On Bispecific Antibodiesmentioning

confidence: 99%

New insights into the pretargeting approach to image and treat tumours

et al. 2016

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Tumour pretargeting is a promising strategy for cancer diagnosis and therapy allowing for the rational use of long circulating, highly specific monoclonal antibodies (mAbs) for both non-invasive cancer radioimmunodetection (RID) and radioimmunotherapy (RIT). In contrast to conventional RID/RIT where the radionuclides and oncotropic vector molecules are delivered as presynthesised radioimmunoconjugates, the pretargeting approach is a multistep procedure that temporarily separates targeting of certain tumour-associated antigens from delivery of diagnostic or therapeutic radionuclides. In principle, unlabelled, highly tumour antigen specific mAb conjugates are, in a first step, administered into a patient. After injection, sufficient time is allowed for blood circulation, accumulation at the tumour site and subsequent elimination of excess mAb conjugates from the body. The small fast-clearing radiolabelled effector molecules with a complementary functionality directed to the prelocalised mAb conjugates are then administered in a second step. Due to its fast pharmacokinetics, the small effector molecules reach the malignant tissue quickly and bind the local mAb conjugates. Thereby, corresponding radioimmunoconjugates are formed in vivo and, consequently, radiation doses are deposited mainly locally. This procedure results in a much higher tumour/non-tumour (T/NT) ratio and is favourable for cancer diagnosis and therapy as it substantially minimises the radiation damage to non-tumour cells of healthy tissues. The pretargeting approach utilises specific non-covalent interactions (e.g. strept(avidin)/biotin) or covalent bond formations (e.g. inverse electron demand Diels-Alder reaction) between the tumour bound antibody and radiolabelled small molecules. This tutorial review descriptively presents this complex strategy, addresses the historical as well as recent preclinical and clinical advances and discusses the advantages and disadvantages of different available variations.

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Section: Recognition Systems Based On Bispecific Antibodiesmentioning

confidence: 99%

New insights into the pretargeting approach to image and treat tumours

et al. 2016

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“…For one, the targeting ligand may be modified. Strategies such as pretargeting , or antibody fragmentation may decrease the circulation time of the 90 Y-labeled agent and as such reduce the associated side effects. Also, a radionuclide with a shorter beta range may be more desirable in murine models, to eliminate cross-fire effects.…”

Section: Discussionmentioning

confidence: 99%

^86/90Y-Based Theranostics Targeting Angiogenesis in a Murine Breast Cancer Model

et al. 2018

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Angiogenesis is widely recognized as one of the hallmarks of cancer. Therefore, imaging and therapeutic agents targeted to angiogenic vessels may be widely applicable in many types of cancer. To this end, the theranostic isotope pair, Y andY, were used to create a pair of agents for targeted imaging and therapy of neovasculature in murine breast cancer models using a chimeric anti-CD105 antibody, TRC105. Serial positron emission tomography imaging with Y-DTPA-TRC105 demonstrated high uptake in 4T1 tumors, peaking at 9.6 ± 0.3%ID/g, verified through ex vivo studies. Additionally, promising results were obtained in therapeutic studies withY-DTPA-TRC105, wherein significantly ( p < 0.05) decreased tumor volumes were observed for the targeted treatment group over all control groups near the end of the study. Dosimetric extrapolation and tissue histological analysis corroborated trends found in vivo. Overall, this study demonstrated the potential of the pair Y for theranostics, enabling personalized treatments for cancer.

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“…Pretargeting has been broadly tested for a variety of blood malignancies in vivo including leukemia (CD45), B cells (CD20, HLA-DR and CD22) and multiple myeoloma (CD38), achieving tumor-to-blood ratios ranging from 2:1 to 638:1, and markedly improved survival rates [36][37][38][39][40][41][42]. These encouraging results in animal models have translated into clinical studies of PRIT, which to date have yielded promising results with reasonable tumor response rates and limited toxicity in phase I/II trials [43,44].…”

Section: Discussionmentioning

confidence: 99%

Pretargeting with bispecific fusion proteins facilitates delivery of nanoparticles to tumor cells with distinct surface antigens

Yang

Parker

Lin

et al. 2017

Journal of Controlled Release

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Tumor heterogeneity, which describes the genetically and phenotypically distinct subpopulations of tumor cells present within the same tumor or patient, presents a major challenge to targeted delivery of diagnostic and/or therapeutic agents. An ideal targeting strategy should deliver a given nanocarrier to the full diversity of cancer cells, which is difficult to achieve with conventional ligand-conjugated nanoparticles. We evaluated pretargeting (i.e., multistep targeting) as a strategy to facilitate nanoparticle delivery to multiple target cells by measuring the uptake of biotinylated nanoparticles by lymphoma cells with distinct surface antigens pretreated with different bispecific streptavidin-scFv fusion proteins. Fusion proteins targeting CD20 or tumor-associated glycoprotein 72 (TAG-72) mediated the specific in vitro uptake of 100nm biotin-functionalized nanoparticles by Raji and Jurkat lymphoma cells (CD20-positive and TAG-72-positive cells, respectively). Greater uptake was observed for pretargeted nanoparticles with increasing amounts of surface biotin, with 6- to 18-fold higher uptake vs. non-biotinylated nanoparticle and fusion protein controls. Fully biotin-modified particles remained resistant to cultured macrophage cell uptake, although they were still quickly cleared from systemic circulation in vivo (t<1h). For single Raji tumor-bearing mice, pretargeting with CD20-specific FP significantly increased nanoparticle tumor targeting. In mice bearing both Raji and Jurkat tumors, pretargeting with both fusion proteins markedly increased nanoparticle targeting to both tumor types, compared to animals dosed with nanoparticles alone. These in vitro and in vivo observations support further evaluations of pretargeting fusion protein cocktails as a strategy to enhance nanoparticle delivery to a diverse array of molecularly distinct target cells.

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Pretargeted radioimmunotherapy: clinically more efficient than conventional radioimmunotherapy?

Cited by 6 publications

References 15 publications

New insights into the pretargeting approach to image and treat tumours

New insights into the pretargeting approach to image and treat tumours

^86/90Y-Based Theranostics Targeting Angiogenesis in a Murine Breast Cancer Model

Pretargeting with bispecific fusion proteins facilitates delivery of nanoparticles to tumor cells with distinct surface antigens

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