Paul Ehrlich — in search of the magic bullet

Winau, Florian; Westphal, Otto; Winau, Rolf

doi:10.1016/j.micinf.2004.04.003

Cited by 141 publications

(71 citation statements)

References 5 publications

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“…As targeted deliveries of therapies become more developed, some have shown clinical, albeit short-lived, success (1,2). The majority of targeted anticancer approaches rely on high-affinity monovalent interactions between a cell-targeted agent (monoclonal or recombinant antibodies and peptides) and a tumor-associated protein to direct therapeutic or imaging payload selectively to the tumors (3)(4)(5).…”

mentioning

confidence: 99%

Heterobivalent ligands target cell-surface receptor combinations in vivo

Josan

Vagner

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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A challenge in tumor targeting is to deliver payloads to cancers while sparing normal tissues. A limited number of antibodies appear to meet this challenge as therapeutics themselves or as drug-antibody conjugates. However, antibodies suffer from their large size, which can lead to unfavorable pharmacokinetics for some therapeutic payloads, and that they are targeted against only a single epitope, which can reduce their selectivity and specificity. Here, we propose an alternative targeting approach based on patterns of cell surface proteins to rationally develop small, synthetic heteromultivalent ligands (htMVLs) that target multiple receptors simultaneously. To gain insight into the multivalent ligand strategy in vivo, we have generated synthetic htMVLs that contain melanocortin (MSH) and cholecystokinin (CCK) pharmacophores that are connected via a fluorescent labeled, rationally designed synthetic linker. These ligands were tested in an experimental animal model containing tumors that expressed only one (control) or both (target) MSH and CCK receptors. After systemic injection of the htMVL in tumor-bearing mice, label was highly retained in tumors that expressed both, compared with one, target receptors. Selectivity was quantified by using ex vivo measurement of Europium-labeled htMVL, which had up to 12-fold higher specificity for dual compared with single receptor expressing cells. This proof-of-principle study provides in vivo evidence that small, rationally designed bivalent htMVLs can be used to selectively target cells that express both, compared with single complimentary cell surface targets. These data open the possibility that specific combinations of targets on tumors can be identified and selectively targeted using htMVLs.receptor targeting | multivalency | cross-linking | gene expression profiling

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mentioning

confidence: 99%

Heterobivalent ligands target cell-surface receptor combinations in vivo

Josan

Vagner

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Furthermore, IPNs are distinguishable from blends, block copolymers, and graft copolymers for two important reasons; firstly, an IPN swells but does not dissolve in solvents, and secondly, the creep and flow is suppressed. Because of its distinguishable features, these biocompatible, nontoxic and biodegradable polymers are acquiring a unique place in various biomedical applications, such as, cartilage scaffolds, biological tissue graft, tissue engineering, wound dressing and for drug delivery [74][75][76].…”

Section: Interpenetrating Polymeric Network Hydrogels As a Topical Drmentioning

confidence: 99%

Temporomandibular Disorders and BIO-IPNs: in vitro approach to find molecular solution to biological problem

Perchyonok¹,

Grobler²,

Basson³

et al. 2016

Nanomaterials and Regenerative Medicine

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“…1 Functional and structural characterization of antibodies culminated in several precedent discoveries on the generation and maturation of the humoral immune response. 2 The key scientific breakthrough that advanced the evaluation of antibodies as therapeutic modalities was the development of hybridoma technology, which afforded the ability to reliably produce sufficient quantities of "monospecific" or identical antibody moieties, i.e., monoclonal antibodies (mAbs).…”

Section: Monoclonal Antibody Therapies For Immune-mediated Disordersmentioning

confidence: 99%