Approaches to improve tumor accumulation and interactions between monoclonal antibodies and immune cells

Marcucci, Fabrizio; Bellone, Matteo; Rumio, Cristiano; Corti, Angelo

doi:10.4161/mabs.22775

Cited by 42 publications

(40 citation statements)

References 120 publications

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“…Poor localization and penetration of monoclonal antibodies (mAb) into solid tumors is one of main mechanisms of limiting tumor response to antibody therapy (1,2). For example, mAb accumulation in tumors of patients is typically very inefficient, in the order of 0.001% to 0.01% of the injected dose per gram of tumor (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…For example, mAb accumulation in tumors of patients is typically very inefficient, in the order of 0.001% to 0.01% of the injected dose per gram of tumor (2)(3)(4). For anticancer mAbs targeting antigens expressed on solid tumors, systemically administered mAbs need to selectively localize to tumor vessels, cross the blood vessels into the tumor parenchyma, and then penetrate into tumor tissues across the interstitium by diffusion or convection to reach as many tumor cells as possible (2)(3)(4). However, the abnormal physiologic and physical properties of solid tumors, such as the defective blood vessels, lack of lymphatic drainage, and extracellular matrix components, limit the extravasation of mAbs from blood vessels and spread within tumor tissues (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

“…Another approach includes the coadministration of mAbs with so-called promoter agents that enhance vascular permeability and/or reduce epithelial barriers, which leads to improved tumor tissue penetration of bloodborne mAbs (reviewed in refs. 2,5). For example, coadministration of an internalizing Arg-Gly-Asp (iRGD) tumor-penetrating peptide (7)(8)(9) and a viral protein called epithelial junction opener-1 (JO-1; ref.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Enhancement of the Tumor Penetration of Monoclonal Antibody by Fusion of a Neuropilin-Targeting Peptide Improves the Antitumor Efficacy

Shin

Sung

Kim

et al. 2014

Molecular Cancer Therapeutics

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The limited localization and penetration of monoclonal antibodies (mAb) into solid tumors restricts their antitumor efficacy. Here, we describe a solid tumor-targeting antibody with enhanced tumor penetration activity. We designed a 22-residue peptide (A22p), which was extracted from the C-terminal basic region of semaphorin 3A (Sema3A) but modified to have higher affinity with neuropilin receptors (NRP), and genetically fused it to the C-terminus of Fc of human immunoglobulin G1 via a 15-residue (G 4 S) 3 linker, generating FcA22p, for the bivalent binding to NRPs. In contrast to Fc or the monovalent A22p peptide alone, Fc-A22p homed to tumor vessels and induced vascular permeability through VE-cadherin downregulation and penetrated tumor tissues by interacting with NRPs in mice bearing human tumor xenografts. We extended the Fc-A22p platform by generating mAb-A22p antibodies of two clinically approved solid tumor-targeting mAbs, the anti-EGF receptor mAb cetuximab (erbitux), and the anti-Her2 mAb trastuzumab (herceptin). The mAb-A22p antibodies retained the intrinsic antigen binding, natural Fc-like biophysical properties, and productivity in mammalian cell cultures, comparable with those of the parent mAbs. In mouse xenograft tumor models, the mAb-A22p antibodies more efficiently homed to tumor vessels and spread into the extravascular tumor parenchyma, which significantly enhanced antitumor efficacy compared with the parent mAbs. Our results suggest that mAb-A22p is a superior format for solid tumor-targeting antibodies due to its enhanced tumor tissue penetration and greater antitumor efficacy compared with conventional mAbs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enhancement of the Tumor Penetration of Monoclonal Antibody by Fusion of a Neuropilin-Targeting Peptide Improves the Antitumor Efficacy

Shin

Sung

Kim

et al. 2014

Molecular Cancer Therapeutics

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“…The unprecedented success of rituximab makes it become a mainstay in the therapy of a broad variety of B-cell NHL [11,12]. However, there are still many patients who present native or acquired resistance to the mAb treatment [13]. Many new anti-CD20 mAbs with gene-engineered modifications have been developed, but to date none of the newer anti-CD20 antibodies have been shown to be clinically more effective than rituximab in a direct comparison [14].…”

Section: Introductionmentioning

confidence: 99%

Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

Xiao

Liu

et al. 2013

Experimental Cell Research

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Biomaterials‐Based Delivery of Therapeutic Antibodies for Cancer Therapy

Wang

Shen

et al. 2021

Adv Healthcare Materials

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Considerable breakthroughs in the treatment of malignant tumors using antibody drugs, especially immunomodulating monoclonal antibodies (mAbs), have been made in the past decade. Despite technological advancements in antibody design and manufacture, multiple challenges face antibody-mediated cancer therapy, such as instability in vivo, poor tumor penetration, limited response rate, and undesirable off-target cytotoxicity. In recent years, an increasing number of biomaterials-based delivery systems have been reported to enhance the antitumor efficacy of antibody drugs. This review summarizes the advances and breakthroughs in integrating biomaterials with therapeutic antibodies for enhanced cancer therapy. A brief introduction to the principal mechanism of antibody-based cancer therapy is first established, and then various antibody immobilization strategies are provided. Finally, the current state-of-the-art in biomaterials-based antibody delivery systems and their applications in cancer treatment are summarized, highlighting how the delivery systems augment the therapeutic efficacy of antibody drugs. The outlook and perspective on biomaterials-based delivery of antitumor antibodies are also discussed.

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Approaches to improve tumor accumulation and interactions between monoclonal antibodies and immune cells

Cited by 42 publications

References 120 publications

Enhancement of the Tumor Penetration of Monoclonal Antibody by Fusion of a Neuropilin-Targeting Peptide Improves the Antitumor Efficacy

Enhancement of the Tumor Penetration of Monoclonal Antibody by Fusion of a Neuropilin-Targeting Peptide Improves the Antitumor Efficacy

Nanoscale mapping and organization analysis of target proteins on cancer cells from B-cell lymphoma patients

Biomaterials‐Based Delivery of Therapeutic Antibodies for Cancer Therapy

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