Antibodies for Effector Cell Redirection

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (20 December 2021) | Viewed by 9057

Special Issue Editors


E-Mail Website
Guest Editor
Division of Stem Cell Transplantation and Immunotherapy, Christian-Albrechts-Universität zu Kiel, Kiel, Germany
Interests: antibody engineering; antibody-based immunotherapy; immune effector cell recruitment; bispecific antibodies; cancer immunotherapy

E-Mail Website
Guest Editor
Protein Engineering and Antibody Technologies Department, Merck KGaA, 64293 Darmstadt, Germany
Interests: antibody hit discovery; antibody engineering; protein engineering; bispecific antibodies; monoclonal antibodies; single domain antibodies; immune cell redirection; immunoligands; antagonistic antibodies; agonistic antibodies; immune checkpoint inhibitors; phage display; yeast surface display; mammalian display; B cell selection strategies

Special Issue Information

Dear Colleagues,

Since the advent of cancer immunotherapy, the field of effector cell-redirecting agents/antibody derivatives has made tremendous progress. Consequently, multiple bispecific antibody derivates that harness the body’s own immune effector cell repertoire are currently being investigated in clinical trials. While traditionally, α/β T cells were the preferred effector cell population for redirection, today, multiple different types of effector cells are being exploited, including (but not limited to) NK cells, γ/δ T cells, macrophages, and neutrophils. Moreover, combinatorial approaches are known to date, involving several different immune cell populations that can be addressed in a direct manner (e.g., by addressing activating receptors or co-stimulatory signals shared by different cell populations) or via secondary effects (such as targeted cytokine release). In addition to triggering activating receptors on effector cells in a tumor-targeted fashion, we understand immune cell redirection in a broader manner, such as conditional blockade of inhibitory receptors or providing co-stimulatory signals within the tumor microenvironment. Beyond bi- and multispecific approaches, the choice of the antibody isotype and Fc engineering in general drastically impact the type of activated effector cell population and hence can be considered as additional aspects of immune cell redirection.

This Special Issue is dedicated to effector cell redirection in its entirety. We invite you to contribute with an original article or a review.

Prof. Dr. Matthias Peipp
Dr. Stefan Zielonka
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibodies is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Antibody engineering 
  • Bispecific antibodies 
  • Multispecific antibodies 
  • Protein engineering 
  • Immunoligands 
  • Antibody Isotypes 
  • Fc engineering 
  • NK cells 
  • T cells 
  • Macrophages 
  • Dendridic cells 
  • Immune cell engagers 
  • Effector cell engagers

Published Papers (1 paper)

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Research

22 pages, 3270 KiB  
Article
Cryopreservation of Natural Killer Cells Pre-Complexed with Innate Cell Engagers
by Uwe Reusch, Kristina Ellwanger, Ivica Fucek, Thomas Müller, Ute Schniegler-Mattox, Joachim Koch and Michael Tesar
Antibodies 2022, 11(1), 12; https://doi.org/10.3390/antib11010012 - 9 Feb 2022
Cited by 6 | Viewed by 7942
Abstract
Innate cell engager (ICE®) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE® constructs with adoptive NK cells is a novel [...] Read more.
Innate cell engager (ICE®) constructs are bispecific tetravalent antibodies targeting specific tumor antigens and simultaneously engaging natural killer (NK) cell and macrophage receptors for the destruction of tumor cells. Pre-complexing of ICE® constructs with adoptive NK cells is a novel approach to enhance NK cell activity. The suitability of such complexes for cryopreservation, whilst retaining the biological activity and specificity, may enable the development of off-the-shelf NK cell products. This study investigates the binding affinity of ICE® constructs targeting EpCAM and NK cell receptors CD16A, NKG2D, or NKp46 to the corresponding antigens, the ICE® antitumor activity, and feasibility of cryopreservation. Cell surface retention assays using primary NK cells confirmed a substantially slower ICE® construct dissociation kinetics compared with control molecules, suggesting the formation of durable complexes independently of the CD16A polymorphism. The high-affinity NK cell and EpCAM/CD16A ICE® complexes were superior to those engaging NKG2D or NKp46 receptors when tested for the NK-cell-mediated elimination of EpCAM-expressing tumor cells. Moreover, the potency and efficacy of these complexes were unaffected after a single freeze–thaw cycle. CD16A-selective ICE® drug candidates complexed with NK cells hold promise as novel cryopreserved off-the-shelf NK cell products with chimeric antigen receptor-like NK cell properties, capable of effective depletion of tumor cells. Full article
(This article belongs to the Special Issue Antibodies for Effector Cell Redirection)
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