Radioimmunoconjugates for treating cancer: recent advances and current opportunities

Bourgeois, Mickaël; Bailly, Clément; Frindel, Mathieu; Guérard, François; Chérel, Michel; Faivre-Chauvet, Alain; Kraeber-Bodéré, Françoise; Bodet-Milin, Caroline

doi:10.1080/14712598.2017.1322577

Cited by 28 publications

(26 citation statements)

References 44 publications

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“…However, to enhance effectiveness of the targeted therapy, one design from logical thinking would be immunoconjugates with cytotoxic agents. The cytotoxic agents may be a chemotherapy drug, a protein toxin, or a radionuclide, thus creating ADCs, 4 immunotoxins, 5,6 or radioimmunoconjugates (RICs), 18 respectively.…”

Section: Immunoconjugates For Cancer Therapymentioning

confidence: 99%

“…By combining the benefit of the specificity of antibodies and the high potency of radiation therapies, researchers developed RICs exhibiting high potency in treating cancers. 18 RICs are mAbs labeled with therapeutic radionuclides which can deliver radiation precisely to the tumor cells or cells with heterogeneously expressed antigens. So far, two RICs targeting CD20 have been approved for treating hematological malignancies, 90 Y-ibritumomab tiuxetan and 131 I-tositumomab.…”

Section: Radioimmunoconjugatesmentioning

confidence: 99%

“…Concerning therapeutic applications, RICs have demonstrated their efficacy in the treatment of both hematological malignancies and solid tumors. 18,25…”

Section: Radioimmunoconjugatesmentioning

confidence: 99%

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Immunotoxins: Targeted Toxin Delivery for Cancer Therapy

Xin

Chen

Wang

et al. 2019

Pharmaceutical Fronts

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Immunotoxins are proteins that consist of a protein toxin conjugated to a specific targeting moiety. The targeting moiety is usually an antibody or ligand, such as monoclonal antibody, antibody fragment, a cytokine, or a growth factor. The toxins usually come from plant toxins, bacterial toxins, or human-origin cytotoxic elements. Nearly all toxins work by enzymatically inhibiting protein synthesis. After binding to antigens or receptors on target cell surfaces, immunotoxins are internalized and translocated to the cytosol where they can kill the cells. Immunotoxins have demonstrated high cytotoxicity to cancer cells and to date two immunotoxins have been approved by U.S. Food and Drug Administration on the markets for the treatment of hematological tumors: Lumoxiti and Ontak. Many other molecules are under development or clinical trials for different forms of cancer. Although immunotoxins exhibit great potency in xenograft model systems and early clinical trials, there are obstacles that limit successful treatments, including immunogenicity, nonspecific toxicity, and poor penetration. However, efforts are underway to address these problems. In this review, we summarize immunotoxins currently in clinical trials for either hematological tumors or solid tumors, outline the design of immunotoxins utilizing variety of components, and discuss the prominent examples of redesigned immunotoxins with reduced immunogenicity and nonspecific toxicity, as well as the strategies in manufacturing immunotoxins. With further improvements, it is anticipated that immunotoxins will play an increasing role in cancer therapy.

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Section: Immunoconjugates For Cancer Therapymentioning

confidence: 99%

Section: Radioimmunoconjugatesmentioning

confidence: 99%

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Immunotoxins: Targeted Toxin Delivery for Cancer Therapy

Xin

Chen

Wang

et al. 2019

Pharmaceutical Fronts

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“…Radioimmunoconjugates have gained interest as important tools in the treatment and management of cancer [1][2][3]. Their use has been applied in both radiotherapy and nuclear molecular imaging through single photon emission computed tomography (SPECT) and positron emission tomography (PET); where gamma emitting or positron emitting radionuclides are linked to a monoclonal antibody (mAb).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a 68Ga-Labeled DOTA-Tetrazine as a PET Alternative to 111In-SPECT Pretargeted Imaging

et al. 2020

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The bioorthogonal reaction between a tetrazine and strained trans-cyclooctene (TCO) has garnered success in pretargeted imaging. This reaction was first validated in nuclear imaging using an 111In-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-linked bispyridyl tetrazine (Tz) ([111In]In-DOTA-PEG11-Tz) and a TCO functionalized CC49 antibody. Given the initial success of this Tz, it has been paired with TCO functionalized small molecules, diabodies, and affibodies for in vivo pretargeted studies. Furthermore, the single photon emission tomography (SPECT) radionuclide, 111In, has been replaced with the β-emitter, 177Lu and α-emitter, 212Pb, both yielding the opportunity for targeted radiotherapy. Despite use of the ‘universal chelator’, DOTA, there is yet to be an analogue suitable for positron emission tomography (PET) using a widely available radionuclide. Here, a 68Ga-labeled variant ([68Ga]Ga-DOTA-PEG11-Tz) was developed and evaluated using two different in vivo pretargeting systems (Aln-TCO and TCO-CC49). Small animal imaging and ex vivo biodistribution studies were performed and revealed target specific uptake of [68Ga]Ga-DOTA-PEG11-Tz in the bone (3.7 %ID/g, knee) in mice pretreated with Aln-TCO and tumor specific uptake (5.8 %ID/g) with TCO-CC49 in mice bearing LS174 xenografts. Given the results of this study, [68Ga]Ga-DOTA-PEG11-Tz can serve as an alternative to [111In]In-DOTA-PEG11-Tz.

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“…In the last decade, a range of directly labeled antibody conjugates have been developed and clinically tested for diagnostic targeting of different tumor entities, including several cetuximab and trastuzumab derivatives . Despite their high affinity and exceptional specificity, such large sized immunoconjugates can face some severe limitations regarding their application as imaging tracer such as slow pharmacokinetics, prolonged blood retention, and poor penetration in solid tumors . By contrast, sdAbs are ideally suited for targeted diagnostic immunoconjugates with intended urinary elimination due to their dimensions in the low nanometer range falling far below the renal filtration threshold as well as excellent antigen targeting performance, fast pharmacokinetics, and sufficient tissue penetration .…”

Section: Introductionmentioning

confidence: 99%

Active Targeting of Dendritic Polyglycerols for Diagnostic Cancer Imaging

Pant

Neuber

Zarschler

et al. 2019

Small

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Active tumor targeting involves the decoration of nanomaterials (NMs) with oncotropic vector biomolecules that selectively recognize certain antigens on malignant cells or in the tumor microenvironment. This strategy can facilitate intracellular uptake of NM through specific interactions such as receptor‐mediated endocytosis and can lead to prolonged retention in the malignant tissues by preventing rapid efflux from the tumor. Here, the design of actively targeting, renally excretible bimodal dendritic polyglycerols (dPGs) for diagnostic cancer imaging is described. Single‐domain antibodies (sdAbs) specifically binding to the epidermal growth factor receptor (EGFR) are employed herein as targeting warheads owing to their small size and high affinity for their corresponding antigen. The dPGs equipped with EGFR‐targeting feature are compared head‐to‐head with their nontargeting counterparts in terms of interaction with EGFR‐overexpressing cells in vitro as well as accumulation at receptor‐positive tumors in vivo. Experimental results reveal a higher specificity and preferential tumor accumulation for the α‐EGFR dPGs, resulting from the introduction of active targeting capabilities on their backbone. These results highlight the potential for improving the tumor uptake properties of dPGs by strategic use of sdAb functionalization, which can ultimately prove useful to the development of ultrasmall NM with highly specific tumor accumulation.

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Radioimmunoconjugates for treating cancer: recent advances and current opportunities

Cited by 28 publications

References 44 publications

Immunotoxins: Targeted Toxin Delivery for Cancer Therapy

Immunotoxins: Targeted Toxin Delivery for Cancer Therapy

Evaluation of a 68Ga-Labeled DOTA-Tetrazine as a PET Alternative to 111In-SPECT Pretargeted Imaging

Active Targeting of Dendritic Polyglycerols for Diagnostic Cancer Imaging

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