Pretargeted Imaging and Radioimmunotherapy of Cancer Using Antibodies and Bioorthogonal Chemistry

Watering, Floor C. J. van de; Rijpkema, Mark; Robillard, Marc S.; Oyen, Wim J.G.; Boerman, Otto C.

doi:10.3389/fmed.2014.00044

Cited by 50 publications

(57 citation statements)

References 48 publications

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“…Many of those aspects are intensively researched with regard to single treatments and reviewed elsewhere. 3,[23][24][25][26][27][28][29] This work focuses on the presentation of pre-clinical and clinical investigations on CIERT as a promising treatment strategy.…”

Section: Combination Of Internal and External Radiotherapymentioning

confidence: 99%

“…The tumour is pre-targeted with the unlabelled complementary prepared antibody, and the radionuclide is delivered via a small molecule recognizing the antibody by the complementary system in a second step. This may lead to higher tumour uptake with lower normal tissue retention (reviewed in van de Watering et al 29 ). However, a combination with EBRT has never been investigated and substantial research on scheduling would be mandatory.…”

Section: Combination Of Internal and External Radiotherapymentioning

confidence: 99%

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Improving external beam radiotherapy by combination with internal irradiation

Dietrich¹,

Koi²,

Zöphel³

et al. 2015

BJR

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The efficacy of external beam radiotherapy (EBRT) is dose dependent, but the dose that can be applied to solid tumour lesions is limited by the sensitivity of the surrounding tissue. The combination of EBRT with systemically applied radioimmunotherapy (RIT) is a promising approach to increase efficacy of radiotherapy. Toxicities of both treatment modalities of this combination of internal and external radiotherapy (CIERT) are not additive, as different organs at risk are in target. However, advantages of both single treatments are combined, for example, precise high dose delivery to the bulk tumour via standard EBRT, which can be increased by addition of RIT, and potential targeting of micrometastases by RIT. Eventually, theragnostic radionuclide pairs can be used to predict uptake of the radiotherapeutic drug prior to and during therapy and find individual patients who may benefit from this treatment. This review aims to highlight the outcome of pre-clinical studies on CIERT and resultant questions for translation into the clinic. Few clinical data are available until now and reasons as well as challenges for clinical implementation are discussed.

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Section: Combination Of Internal and External Radiotherapymentioning

confidence: 99%

Section: Combination Of Internal and External Radiotherapymentioning

confidence: 99%

Improving external beam radiotherapy by combination with internal irradiation

Dietrich¹,

Koi²,

Zöphel³

et al. 2015

BJR

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“…[51][52][53][54][55][56][57][58][59][60] Although remissions have been achieved in most patients, the lack of well-controlled studies makes it difficult to know whether inclusion of radiolabeled antibodies indeed improves outcomes of HCT. 8,61 More recently, "pretargeted" strategies that separate the targeting vehicle from the subsequently administered radioisotope 62,63 (shown in preclinical models to improve tumor/organ ratios of absorbed radioactivity) are clinically investigated as a means to optimize delivery of radiation during transplant conditioning. 64 In parallel, limited efforts have been undertaken to use ␣-emitting antibodies outside the HCT setting (Table 5).…”

Section: Immunotoxinsmentioning

confidence: 99%

Antigen-specific immunotherapies for acute myeloid leukemia

Buckley

Walter

2015

Hematology

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Antigen-specific immunotherapies have emerged as important components of curative treatment algorithms for many cancers. In acute myeloid leukemia (AML), success has been less obvious. Nonetheless, among the few drugs shown to improve survival in recent randomized trials is the CD33 antibody-drug conjugate gemtuzumab ozogamicin. Significant antileukemic activity is also well documented for radioimmunoconjugates targeting CD33, CD45, or CD66. These therapeutics can intensify conditioning before hematopoietic cell transplantation, but their effect on patient outcomes needs clarification. Emerging data now suggest clinical antileukemic activity of several novel antibodies and perhaps some adoptive T-cell immunotherapies and vaccines. In parallel, numerous other agents targeting a wider variety of antigens are currently being explored. However, the antigenic heterogeneity characteristic of AML is a considerable limitation for all these therapeutics, and many important questions related to the ideal target antigen(s), disease situation in which to use these therapies, most suitable patient populations, exact treatment modalities, and details of supportive care needs remain open. Addressing such questions in upcoming studies will be required to ensure that antigen-directed therapies become an effective tool in AML, a disease for which outcomes with standard "3 ϩ 7"-based chemotherapy have remained unsatisfactory in many patients. Learning Objectives• To gain an overview of current clinical results with antigenspecific immunotherapies for acute myeloid leukemia • To become familiar with recent advances and evolving treatment concepts in the field of antigen-specific immunotherapy for acute myeloid leukemia and to appreciate the challenges in the clinical translation of these therapeutic strategies Conceptually, antigen-specific immunotherapies offer a versatile means of eliminating tumor cells with limited nonspecific toxicities. For many human cancers, including some hematological malignancies, such therapies have emerged as important components of curative treatment algorithms. 1-3 Success has been more modest for acute myeloid leukemia (AML). Nonetheless, among the few drugs that have shown to improve survival in recent randomized trials is the CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO). The clinical experience with GO provides the strongest glimpse thus far of the potential value of antigen-targeted therapies for AML. Here, we review the results of efforts with antibodies and other antigen-directed passive and active immunotherapies in AML and summarize evolving treatment strategies for this disease.

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“…In vivo pretargeting approaches could circumvent these issues by harnessing the high specificity and affinity of radioimmunoconjugates while simultaneously avoiding their sluggish pharmacokinetics and high background doses 19. To achieve this, pretargeting strategies decouple the antibody from the radioisotope at the time of injection and combine these two components within the body.…”

Section: Introductionmentioning

confidence: 99%

A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer

Adumeau¹,

Carnazza²,

Brand³

et al. 2016

Theranostics

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The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans-cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a 64Cu-labeled tetrazine radioligand (64Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful clinical tool.

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Pretargeted Imaging and Radioimmunotherapy of Cancer Using Antibodies and Bioorthogonal Chemistry

Cited by 50 publications

References 48 publications

Improving external beam radiotherapy by combination with internal irradiation

Improving external beam radiotherapy by combination with internal irradiation

Antigen-specific immunotherapies for acute myeloid leukemia

A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer

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