Cell-based reporter assays for measurements of antibody-mediated cellular cytotoxicity and phagocytosis against SARS-CoV-2 spike protein

Hong, Yuting; Guo, Hao; Wei, Min; Zhang, Yali; Fang, Mujin; Cheng, Tong; Li, Zhiyong; Ge, Shengxiang; Yao, Xiangyang; Yuan, Quan; Xia, Ningshao

doi:10.1016/j.jviromet.2022.114564

Cited by 11 publications

(10 citation statements)

References 53 publications

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“…Therefore, we next tested the natural killer-dependent antibody-mediated cell cytotoxicity (ADCC) function of the mnAbs as compared with the parental nAbs. 6 As expected, the multivalent transformation promoted ADCC for all 3 antibodies by enhancing avidity binding to Fc receptors (Supplementary Fig. 8e, f ).…”

supporting

confidence: 72%

Nanoparticle-based multivalent human antibodies offer potent and broad neutralization against Omicron sublineages

Wang,

Song,

Wang

et al. 2023

Sig Transduct Target Ther

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supporting

confidence: 72%

Nanoparticle-based multivalent human antibodies offer potent and broad neutralization against Omicron sublineages

Wang,

Song,

Wang

et al. 2023

Sig Transduct Target Ther

Self Cite

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“…On the other hand, the Fc domain of FTL004 was engineered (S240D/I333E mutation) to elevate the affinity to human Fcγ receptors, leading to the enhancement of antibody-dependent cellular cytotoxicity (ADCC) [ 10 ]. In ADCC bioassays with Jurkat-Lucia-CD16a-NFAT cells [ 11 ], FTL004 showed a distinctly higher intensity of ADCC, with EC50 values of 2–8 ng/mL, compared with daratumumab and isatuximab (Fig. 2 c).…”

Section: To the Editormentioning

confidence: 99%

FTL004, an anti-CD38 mAb with negligible RBC binding and enhanced pro-apoptotic activity, is a novel candidate for treatments of multiple myeloma and non-Hodgkin lymphoma

et al. 2022

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Anti-CD38 monoclonal antibodies (mAbs), daratumumab, and isatuximab have represented a breakthrough in the treatment of multiple myeloma (MM). Recently, CD38-based mAbs were expected to achieve increasing potential beyond MM, which encouraged us to develop new anti-CD38 mAbs to meet clinical needs. In this study, we developed a novel humanized anti-CD38 antibody, FTL004, which exhibited enhanced pro-apoptotic ability and negligible binding to red blood cells (RBCs). FTL004 presented a better ability to induce direct apoptosis independent of Fc-mediated cross-linking against lymphoma and MM cell lines as well as primary myeloma cells derived from MM patients. For instance, FTL004 induced RPMI 8226 cells with 55% early apoptosis cells compared with 20% in the isatuximab-treated group. Of interest, FTL004 showed ignorable binding to CD38 on human RBCs in contrast to tumor cells, even at concentrations up to 30 μg/mL. Furthermore, with an engineered Fc domain, FTL004 displayed stronger antibody-dependent cellular cytotoxicity (ADCC) against CD38+ malignant cells. In vivo MM and non-Hodgkin lymphoma tumor xenograft models showed that FTL004 possessed an effective anti-tumor effect. Cryo-electron microscopy structure resolved two epitope centers of FTL004 on CD38: one of which was unique while the other partly overlapped with that of isatuximab. Taken together, FTL004 distinguishes it from other CD38 targeting mAbs and represents a potential candidate for the treatment of MM and non-Hodgkin lymphoma.

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“…The plates were incubated in a 5% CO 2 incubator at 37 • C for 1 h, then the cells were washed once to remove unbinding VHH-Fc. The reporter cells Jurkat-Lucia™ NFAT-CD16 cells or Jurkat-Lucia™ NFAT-CD32 were added and the experiment was performed as described previously [55]. The analysis included positive control (SD38-Fc), negative control (corresponding VHHs without Fc-fragment and non-relevant VHH-Fc), and intact cells.…”

Section: In Vitro Adcc and Adcp Reporter Assaymentioning

confidence: 99%

Cross-Reactive Fc-Fused Single-Domain Antibodies to Hemagglutinin Stem Region Protect Mice from Group 1 Influenza a Virus Infection

Voronina¹,

Shcheblyakov²,

Favorskaya

et al. 2022

Viruses

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The continued evolution of influenza viruses reduces the effectiveness of vaccination and antiviral drugs. The identification of novel and universal agents for influenza prophylaxis and treatment is an urgent need. We have previously described two potent single-domain antibodies (VHH), G2.3 and H1.2, which bind to the stem domain of hemagglutinin and efficiently neutralize H1N1 and H5N2 influenza viruses in vivo. In this study, we modified these VHHs with Fc-fragment to enhance their antiviral activity. Reformatting of G2.3 into bivalent Fc-fusion molecule increased its in vitro neutralizing activity against H1N1 and H2N3 viruses up to 80-fold and, moreover, resulted in obtaining the ability to neutralize H5N2 and H9N2 subtypes. We demonstrated that a dose as low as 0.6 mg/kg of G2.3-Fc or H1.2-Fc administered systemically or locally before infection could protect mice from lethal challenges with both H1N1 and H5N2 viruses. Furthermore, G2.3-Fc reduced the lung viral load to an undetectable level. Both VHH-Fc antibodies showed in vivo therapeutic efficacy when delivered via systemic or local route. The findings support G2.3-Fc as a potential therapeutic agent for both prophylaxis and therapy of Group 1 influenza A infection.

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Cell-based reporter assays for measurements of antibody-mediated cellular cytotoxicity and phagocytosis against SARS-CoV-2 spike protein

Cited by 11 publications

References 53 publications

Nanoparticle-based multivalent human antibodies offer potent and broad neutralization against Omicron sublineages

Nanoparticle-based multivalent human antibodies offer potent and broad neutralization against Omicron sublineages

FTL004, an anti-CD38 mAb with negligible RBC binding and enhanced pro-apoptotic activity, is a novel candidate for treatments of multiple myeloma and non-Hodgkin lymphoma

Cross-Reactive Fc-Fused Single-Domain Antibodies to Hemagglutinin Stem Region Protect Mice from Group 1 Influenza a Virus Infection

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