Specific Targeting of Cancer with siRNA, CRISPR Cas and Antibodies

A special issue of Antibodies (ISSN 2073-4468). This special issue belongs to the section "Antibody-Based Therapeutics".

Deadline for manuscript submissions: closed (20 March 2023) | Viewed by 2422

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Helmholtz-Centre for Infection Research, Structure and Function of Proteins, Inhoffenstraße 7, D-38124 Braunschweig, Germany
Interests: antibody engineering; selection of human antibodies; cancer therapy; intracellular antibodies
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Special Issue Information

Dear Colleagues,

Cancer cells are characterized by overexpression of tumor-associated antigens (TAAs) or tumor-specific neoantigens. Cell-surface-expressed TAAs and neoantigens are particularly targeted by recombinant antibodies to activate the immune system, and some recombinant antibodies with fused effector molecules are able to eliminate tumor cells directly. Neoantigens enhancing tumor growth are mainly expressed inside tumor cells and are now very promising targets for intracellular antibodies, CRISPR Cas, and siRNA. Studies on cellular and animal models and clinical approaches have shown that these knockdown/knockout techniques can be effective in treating cancers. Tumor-cell-specific delivery can be achieved using new recombinant AAVs selected by direct evolution or AAVs with modified capsids comprising incorporated DARPins, nanobodies, or receptor-specific peptides. In addition, tumor-specific nanoparticles with recombinant antibody fragments are in the pipeline. New developments in the CRISPR/Cas system and RNAi to avoid off-target effects and design of first clinical trials with intrabodies will lead to effective next-generation gene therapies.

Dr. Thomas Böldicke
Guest Editor

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Keywords

  • tumor specific targeting
  • adeno associated virus
  • nanoparticle
  • tumor associated antigens
  • neoantigens
  • siRNA
  • CRISPR Cas
  • intrabodies

Published Papers (1 paper)

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Research

13 pages, 5031 KiB  
Article
An Antibody Targeting Fibroblast Activation Protein Simultaneously Fused to Interleukin-2 and Tumor Necrosis Factor Selectively Localizes to Neoplastic Lesions
by Eleonora Prodi, Claudia Comacchio, Ettore Gilardoni, Cesare Di Nitto, Emanuele Puca, Dario Neri and Roberto De Luca
Antibodies 2023, 12(2), 29; https://doi.org/10.3390/antib12020029 - 14 Apr 2023
Cited by 1 | Viewed by 2106
Abstract
The delivery of specific cytokine payloads to a neoplastic environment employing antibodies able to selectively accumulate at the tumor site represents an attractive strategy to stimulate an immune response to cancer. Whilst conventional antibody–cytokine fusions based on a single payload have shown potent [...] Read more.
The delivery of specific cytokine payloads to a neoplastic environment employing antibodies able to selectively accumulate at the tumor site represents an attractive strategy to stimulate an immune response to cancer. Whilst conventional antibody–cytokine fusions based on a single payload have shown potent anticancer activity, the concomitant delivery of two cytokine payloads may further improve the therapeutic outcome as the immune system typically adopts multiple signals to reinforce an antitumor strategy. We here describe a potency-matched dual-cytokine antibody fusion protein containing a tumor-targeting antibody fragment specific to human fibroblast activation protein (FAP), simultaneously linked to both interleukin-2 (IL2) and a tumor necrosis factor (TNF) mutant. The resulting fusion protein, termed IL2-7NP2-TNFmut, formed stable non-covalent trimers driven by the interaction of the tumor necrosis factor subunits. Both cytokine payloads retained their biological activity within the fusion protein, as shown by in vitro cellular assays. The tumor-targeting properties and the anticancer activity of IL2-7NP2-TNFmut were investigated in vivo in immunocompromised mice bearing SKRC52 cells transduced with human FAP. The fusion protein preferentially localized to the cancer site and induced partial tumor retardation. Full article
(This article belongs to the Special Issue Specific Targeting of Cancer with siRNA, CRISPR Cas and Antibodies)
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