Recombinant Antibodies to Arm Cytotoxic Lymphocytes in Cancer Immunotherapy

Koch, Joachim; Tesar, Michael

doi:10.1159/000479981

Cited by 20 publications

(29 citation statements)

References 152 publications

(220 reference statements)

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“…Instead, designed libraries are usually produced and screened for Abs with desired properties. Examples of recombinant Abs are numerous, including therapeutic Abs and various immunoassays [108][109][110][111]. Table 3 shows examples of therapeutic Abs for treating human diseases.…”

Section: Recombinant Antibodiesmentioning

confidence: 99%

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Peptides, Antibodies, Peptide Antibodies and More

Trier

Hansen

Houen

2019

IJMS

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The applications of peptides and antibodies to multiple targets have emerged as powerful tools in research, diagnostics, vaccine development, and therapeutics. Antibodies are unique since they, in theory, can be directed to any desired target, which illustrates their versatile nature and broad spectrum of use as illustrated by numerous applications of peptide antibodies. In recent years, due to the inherent limitations such as size and physical properties of antibodies, it has been attempted to generate new molecular compounds with equally high specificity and affinity, albeit with relatively low success. Based on this, peptides, antibodies, and peptide antibodies have established their importance and remain crucial reagents in molecular biology.

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Section: Recombinant Antibodiesmentioning

confidence: 99%

“…), Abs with several specificities (bispecific, tri-specific, etc.) [110,[115][116][117]. Abs have also been used to convey particular specificities to effector T cells with good effects in the form of chimeric antigen receptor T cells (CARTs) [118].…”

Section: Engineered and Designed Antibodiesmentioning

confidence: 99%

Peptides, Antibodies, Peptide Antibodies and More

Trier

Hansen

Houen

2019

IJMS

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“…By contrast, many tumors are characterized by heterogeneity in expression levels of tumor antigens or their downregulation as a common principle of tumor immune evasion; thus, the degree of avidity and power of ADCC is limited through lower and variable opsonization of tumor target cells with immunoglobulins. 9 Evidence from numerous studies supports the rationale of employing efficient NK cell engagement to achieve therapeutic benefits: In vivo, mice that have been NK cell-depleted or harbor NK cell deficiencies have a several-fold increased incidence of spontaneous or carcinogen-induced tumors. [10][11][12] These findings are reflected in humans where abnormal cytolytic function of NK cells is associated with a severely increased risk to develop several types of malignancies, especially hematologic cancers.…”

Section: Introductionmentioning

confidence: 99%

Redirected optimized cell killing (ROCK®): A highly versatile multispecific fit-for-purpose antibody platform for engaging innate immunity

Ellwanger

Reusch

Fucek

et al. 2019

mAbs

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Redirection of immune cells to efficiently eliminate tumor cells holds great promise. Natural killer cells (NK), macrophages, or T cells are specifically engaged with target cells expressing markers after infection or neoplastic transformation, resulting in their activation and subsequent killing of those targets. Multiple strategies to redirect immunity have been developed in the past two decades, but they have technical hurdles or cause undesirable side-effects, as exemplified by the T cell-based chimeric antigen receptor approaches (CAR-T therapies) or bispecific T cell engager platforms. Our first-in-class bispecific antibody redirecting innate immune cells to tumors (AFM13, a CD30/CD16A-specific innate immune cell engager) has shown signs of clinical efficacy in CD30-positive lymphomas and the potential to be safely administered, indicating a wider therapeutic window compared to T cell engaging therapies. AFM13 is the most advanced candidate from our fit-for-purpose redirected optimized cell killing (ROCK®) antibody platform, which comprises a plethora of CD16A-binding innate immune cell engagers with unique properties. Here, we discuss aspects of this modular platform, including the advantages of innate immune cell engagement over classical monoclonal antibodies and other engager concepts. We also present details on its potential to engineer a fit-for-purpose innate immune cell engager format that can be equipped with unique CD16A domains, modules that influence pharmacokinetic properties and molecular architectures that influence the activation of immune effectors, as well as tumor targeting. The ROCK® platform is aimed at the activation of innate immunity for the effective lysis of tumor cells and holds the promise of overcoming limitations of other approaches that redirect immune cells by widening the therapeutic window.

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“…The relative contribution of these mechanisms of action to the therapeutic efficacy of rituximab and other mAbs has not been fully established, although ADCC is thought to be the main mechanism underlying their efficacies [24]. Recently, a new generation of NK cell-activating antibodies has been developed [25]. Particularly, bispecific and trispecific killer cell engagers (BiKEs and TRiKEs) that stimulate NK cells against one or more tumor antigens are promising agents that are in preclinical and initial clinical studies [25][26][27].…”

Section: Nk Cell-based Therapiesmentioning

confidence: 99%

Mechanisms of Resistance to NK Cell Immunotherapy

Sordo‐Bahamonde

Vitale

Lorenzo‐Herrero

et al. 2020

Cancers

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Immunotherapy has recently been a major breakthrough in cancer treatment. Natural killer (NK) cells are suitable targets for immunotherapy owing to their potent cytotoxic activity that may target cancer cells in a major histocompatibility complex (MHC) and antigen-unrestricted manner. Current therapies targeting NK cells include monoclonal antibodies that promote NK cell antibody-dependent cell-mediated cytotoxicity (ADCC), hematopoietic stem cell transplantation (HSCT), the adoptive transfer of NK cells, the redirection of NK cells using chimeric antigen receptor (CAR)-NK cells and the use of cytokines and immunostimulatory drugs to boost the anti-tumor activity of NK cells. Despite some encouraging clinical results, patients receiving these therapies frequently develop resistance, and a myriad of mechanisms of resistance affecting both the immune system and cancer cells have been reported. A first contributing factor that modulates the efficacy of the NK cell therapy is the genetic profile of the individual, which regulates all aspects of NK cell biology. Additionally, the resistance of cancer cells to apoptosis and the immunoediting of cancer cells, a process that decreases their immunogenicity and promotes immunosuppression, are major determinants of the resistance to NK cell therapy. Consequently, the efficacy of NK cell anti-tumor therapy is specific to each patient and disease. The elucidation of such immunosubversive mechanisms is crucial to developing new procedures and therapeutic strategies to fully harness the anti-tumor potential of NK cells.

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Recombinant Antibodies to Arm Cytotoxic Lymphocytes in Cancer Immunotherapy

Cited by 20 publications

References 152 publications

Peptides, Antibodies, Peptide Antibodies and More

Peptides, Antibodies, Peptide Antibodies and More

Redirected optimized cell killing (ROCK®): A highly versatile multispecific fit-for-purpose antibody platform for engaging innate immunity

Mechanisms of Resistance to NK Cell Immunotherapy

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