ADCC enhancement: A conundrum or a boon to mAb therapy?

Narvekar, Aditya; Pardeshi, Apurva; Jain, Rekha; Dandekar, Prajakta

doi:10.1016/j.biologicals.2022.08.006

Cited by 3 publications

(2 citation statements)

References 52 publications

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“…ADCC is an adaptive immune response mainly composed of NK cells passing through CD16A (FcγRIIIA) receptor-mediated binding to the Fc portion of IgG antibodies, triggering target cell lysis [25]. PBMCs include lymphocytes (T cells, B cells, and NK cells), monocytes, and dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Diagnostic and Therapeutic Potential of a T Cell Receptor (TCR)-like single Domain Antibody (sDAb)-Human IgG1 Antibody against Heat Shock Protein (HSP) 16KDa/HLA-A2 for Latent Tuberculosis

Liu,

Dass,

Wong

et al. 2024

TropicalMed

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Heat shock protein 16-kDa (HSP 16-kDa) is essential for the survival of Mycobacterium tuberculosis (M. tuberculosis) during the latent period; hence, a peptide–MHC presentation of HSP 16-kDa could be a potential diagnostic and therapeutic target for latent tuberculosis (LTB). This study aimed to generate a TCR-like single-domain antibody (sDAb)-human IgG1 antibody and subsequently investigate its diagnostic and therapeutic potential in LTB, utilizing a model cell presenting the target peptide. A previously generated TCR-like sDAB that can bind to HSP 16-kDa was first fused to a human IgG1 Fc-receptor via a linker. The fusion product, sDAb-IgG1, was expressed with HEK293-F and was subsequently purified. Its diagnostic potential was investigated via cell-based ELISA utilizing MCF-7 cells peptide-pulsed with HSP 16-kDa peptides. Investigation into the antibody-dependent cell-mediated cytotoxicity (ADCC) of MCF-7 cells was also conducted to investigate its therapeutic potential. Finally, TCR-like sDAb-IgG1 was successfully produced transiently with HEK-293F and was purified using protein A chromatography. The generated antibody was tested using cell-based ELISA, which demonstrated the effective binding of the TCR-like sDAb-IgG1 to the 16-kDa peptide–MHC on the cell surface. The ADCC assay also showed that the antibody effectively mediated the ADCC of MCF-7 cells with the help of 16-kDa peptide–MHC. This allows us to hypothesize the possible utility of the said antibody for both diagnostics and therapeutics of latent tuberculosis after more investigations with clinical samples.

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Section: Discussionmentioning

confidence: 99%

Investigating the Diagnostic and Therapeutic Potential of a T Cell Receptor (TCR)-like single Domain Antibody (sDAb)-Human IgG1 Antibody against Heat Shock Protein (HSP) 16KDa/HLA-A2 for Latent Tuberculosis

Liu,

Dass,

Wong

et al. 2024

TropicalMed

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“…The therapeutic effect of targeted antibodies similar to patritumab deruxtecan may be due to antibody-dependent cellular cytotoxicity (ADCC) rather than any direct intracellular interactions presumed to take place after cell binding [ 113 ]. ADCC is an immune-mediated cytotoxic response that can be leveraged against a tumor cell through recognition between the FCgamma receptor R on effector cells and the Fc region of antibodies bound to cancer cells [ 114 ]. Other mAbs such as zenocutuzumab and seribantumab are both in Phase 2 clinical trials to treat NRG1-fusion+ solid tumors.…”

Section: Penton Base-derived Macromolecular Delivery By Herpbk10 (Hpk)mentioning

confidence: 99%

Adenovirus-Derived Nano-Capsid Platforms for Targeted Delivery and Penetration of Macromolecules into Resistant and Metastatic Tumors

Benhaghnazar

Medina-Kauwe

2023

Cancers

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Macromolecular therapeutics such as nucleic acids, peptides, and proteins have the potential to overcome treatment barriers for cancer. For example, nucleic acid or peptide biologics may offer an alternative strategy for attacking otherwise undruggable therapeutic targets such as transcription factors and similar oncologic drivers. Delivery of biological therapeutics into tumor cells requires a robust system of cell penetration to access therapeutic targets within the cell interior. A highly effective means of accomplishing this may be borrowed from cell-penetrating pathogens such as viruses. In particular, the cell entry function of the adenovirus penton base capsid protein has been effective at penetrating tumor cells for the intracellular deposition of macromolecular therapies and membrane-impermeable drugs. Here, we provide an overview describing the evolution of tumor-targeted penton-base-derived nano-capsids as a framework for discussing the requirements for overcoming key barriers to macromolecular delivery. The development and pre-clinical testing of these proteins for therapeutic delivery has begun to also uncover the elusive mechanism underlying the membrane-penetrating function of the penton base. An understanding of this mechanism may unlock the potential for macromolecular therapeutics to be effectively delivered into cancer cells and to provide a treatment option for tumors resisting current clinical therapies.

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Selenium nanoparticles enhance the anti-tumor immune responses of anti-4-1BB antibody and alleviate the adverse effects on mice

zhang,

Liu,

Shen

et al. 2024

Immunobiology

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ADCC enhancement: A conundrum or a boon to mAb therapy?

Cited by 3 publications

References 52 publications

Investigating the Diagnostic and Therapeutic Potential of a T Cell Receptor (TCR)-like single Domain Antibody (sDAb)-Human IgG1 Antibody against Heat Shock Protein (HSP) 16KDa/HLA-A2 for Latent Tuberculosis

Investigating the Diagnostic and Therapeutic Potential of a T Cell Receptor (TCR)-like single Domain Antibody (sDAb)-Human IgG1 Antibody against Heat Shock Protein (HSP) 16KDa/HLA-A2 for Latent Tuberculosis

Adenovirus-Derived Nano-Capsid Platforms for Targeted Delivery and Penetration of Macromolecules into Resistant and Metastatic Tumors

Selenium nanoparticles enhance the anti-tumor immune responses of anti-4-1BB antibody and alleviate the adverse effects on mice

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