Therapy for colon carcinoma xenografts with bispecific antibody-targeted, iodine-131-labeled bivalent hapten

Gautherot, B S Emmanuel; Bouhou, B S Jamila; Doussal, Jean-Marc Le; Manetti, Corine; Martin, Bernadette; Rouvier, Éric; Barbet, Jacques

doi:10.1002/(sici)1097-0142(19971215)80:12+<2618::aid-cncr37>3.0.co;2-d

Cited by 37 publications

(28 citation statements)

References 7 publications

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“…A second variant of this approach also uses bsAbs bearing 2 different Fab9 fragments but uses a bivalent radioligand to drive tumoral uptake ( Fig. 3B) (14). Bivalent haptens can bind to 2 bsAbs occupying adjacent antigens on the tumor surface, thereby cross-linking the immunoconjugates and increasing the avidity of binding.…”

Section: Approach 2: Bispecific Antibodiesmentioning

confidence: 99%

Pretargeted Imaging and Therapy

et al. 2017

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In vivo pretargeting stands as a promising approach to harnessing the exquisite tumor-targeting properties of antibodies for nuclear imaging and therapy while simultaneously skirting their pharmacokinetic limitations. The core premise of pretargeting lies in administering the targeting vector and radioisotope separately and having the 2 components combine within the body. In this manner, pretargeting strategies decrease the circulation time of the radioactivity, reduce the uptake of the radionuclide in healthy nontarget tissues, and facilitate the use of short-lived radionuclides that would otherwise be incompatible with antibody-based vectors. In this short review, we seek to provide a brief yet informative survey of the 4 preeminent mechanistic approaches to pretargeting, strategies predicated on streptavidin and biotin, bispecific antibodies, complementary oligonucleotides, and bioorthogonal click chemistry.

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Section: Approach 2: Bispecific Antibodiesmentioning

confidence: 99%

Pretargeted Imaging and Therapy

et al. 2017

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“…"affinity enhancement system" or AES). The bivalent effectors used successfully include AcLys(In-DTPA)-Tyr-Lys(In-DTPA)-Lys(TscG-Cys-)-NH 2 (7,9), Janus bivalent hapten (10), pGlu-Leu-Tyr-Glu-AsnLys(DTPA)-Pro-Arg-Arg-Pro-Tyr-Ile-Leu and DTPA-GlyGlu-Leu-Tyr-Glu-Asn-Lys(Ac)-Pro-Arg-Arg-Pro-Tyr-IleLeu (DTPA-Gly-NT) (11), and Ac-Phe-Lys(-DTPA)-TyrLys(DTPA)-NH 2 (12) and have been variously radiolabeled with 99m Tc, 188 Re, 125 I, 131 I, 111 In, and most recently 68 Ga for radioimmunodetection and radiotherapy in tumor animal models (7,(13)(14)(15)(16). One observation from these investigations has been the importance of molecular spacing between binding sites.…”

Section: Introductionmentioning

confidence: 99%

Affinity Enhancement Bivalent Morpholinos for Pretargeting: Surface Plasmon Resonance Studies of Molecular Dimensions

Liu

Zhang

et al. 2005

Bioconjugate Chem.

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Bivalent effectors have been reported to provide superior pretargeting by affinity enhancement. We recently reported that one bivalent MORF (phosphorodiamidate morpholino, a DNA analogue oligomer) exhibited affinity enhancement (ratio of bivalent to monovalent equilibrium constants for binding) to immobilized complementary DNA (cDNA) by surface plasmon resonance (SPR). Because bivalent effectors using oligomers are easily synthesized with molecular spacing between binding sites, an important determinant of binding, adjustable simply by selecting linkers of different dimensions and/or lengthening or shortening the oligomer chain length, they may have advantages over existing bivalent effectors. We synthesized four bivalent MORFs with different dimensions between binding sites and measured binding affinities and affinity enhancement by SPR. An 18 mer (MORF18) was made bivalent by dimerizing both with disuccinimidyl suberate (DSS) and disuccinimidyl glutarate (DSG) linkers. By again using DSS but adding seven nonbinding adenine bases and by eliminating six binding bases, a total of four bivalent effectors, DSS-MORF12, DSG-MORF18, DSS-MORF18, and DSS-MORF25, were prepared with two different hybridization affinities (i.e. MORF12 and MORF18/25) and three different spacings (i.e. 20, 25, and 100 angstroms) between binding sites. The biotinylated cDNA was immobilized on a sensor chip at 500 and 100 RU coating densities providing an average cDNA separation of 25 and 80 angstroms. As expected, bimolecular binding dominated monomolecular binding in all cases, especially at lower MORF effector concentrations and at higher coating densities. All bivalent MORFs showed equilibrium constants superior to their monovalent form and therefore affinity enhancement. DSS-MORF25 showed the highest equilibrium constant for bimolecular binding presumably because of its larger separation between binding sites. Nevertheless, DSS-MORF12 showed the largest affinity enhancement of almost 3 orders of magnitude presumably because the shorter chain lowered the equilibrium constant for monomolecular binding. We have shown that bivalent effectors may be easily synthesized using MORF. The results provide further evidence that the use of bivalent effectors can greatly improve MORF pretargeting and, finally, that bivalent MORFs with reduced equilibrium constants may actually exhibit higher affinity enhancement.

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“…1) and, therefore, a longer tumor residence time. In animal models, pretargeting using an anti-CEA Fab' x anti-DTPA Fab' bsMAb followed by an 131 I-labeled peptide successfully cured 7/12 animals with less toxicity compared to progressive growth of all tumors in animals given 131 I-labeled anti-CEA F(ab') 2 [34]. Clinical trials using the AES pretargeting method with a chemically constructed bispecific anti-carcinoembryonic antigen (CEA) × anti-indium-DTPA conjugate and a radioiodinated ( 131 I) di-indium-DTPA hapten (Pentacea, IBC Pharmaceuticals) have produced impressive images of tumor uptake with a tumor/whole-body radiation dose advantage of >38 [16], confirming the advantage of this pretargeting method in patients with CEA-expressing neoplasms.…”

Section: Pretargeting With the Bispecific Antibody Recognition Systemmentioning

confidence: 99%

Radioimmunotherapy: Is avidin-biotin pretargeting the preferred choice among pretargeting methods?

Goldenberg

Chang

Sharkey

et al. 2003

Eur J Nucl Med Mol Imaging

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Therapy for colon carcinoma xenografts with bispecific antibody-targeted, iodine-131-labeled bivalent hapten

Cited by 37 publications

References 7 publications

Pretargeted Imaging and Therapy

Pretargeted Imaging and Therapy

Affinity Enhancement Bivalent Morpholinos for Pretargeting: Surface Plasmon Resonance Studies of Molecular Dimensions

Radioimmunotherapy: Is avidin-biotin pretargeting the preferred choice among pretargeting methods?

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