2022
DOI: 10.4049/jimmunol.2100970
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Multifunctional NK Cell–Engaging Antibodies Targeting EGFR and NKp30 Elicit Efficient Tumor Cell Killing and Proinflammatory Cytokine Release

Abstract: In this work, we have generated novel Fc-comprising NK cell engagers (NKCEs) that bridge human NKp30 on NK cells to human epidermal growth factor receptor (EGFR) on tumor cells. Camelid-derived VHH single-domain Abs specific for human NKp30 and a humanized Fab derived from the EGFR-specific therapeutic Ab cetuximab were used as binding arms. By combining camelid immunization with yeast surface display, we were able to isolate a diverse panel of NKp30-specific VHHs against different epitopes on NKp30. Intriguin… Show more

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Cited by 24 publications
(20 citation statements)
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“…For this, we focused on VHHs that address distinct epitopes and elicit a robust activation of NK cells. Similar to what has been shown by Vivier for NKp46 (Gauthier et al, 2019) and our group for NKp30 (Klausz et al, 2022; Pekar et al, 2021), co‐engagement of FcγRIIIa by utilizing an effector functional Fc portion enhanced killing capacities of VHH‐based NKCEs.…”
Section: Discussionsupporting
confidence: 85%
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“…For this, we focused on VHHs that address distinct epitopes and elicit a robust activation of NK cells. Similar to what has been shown by Vivier for NKp46 (Gauthier et al, 2019) and our group for NKp30 (Klausz et al, 2022; Pekar et al, 2021), co‐engagement of FcγRIIIa by utilizing an effector functional Fc portion enhanced killing capacities of VHH‐based NKCEs.…”
Section: Discussionsupporting
confidence: 85%
“…Our group recently described that killing capacities of NKp30‐directed EGFR‐targeting bispecific NKCEs can be further enhanced by co‐triggering FcγRIIIa (Klausz et al, 2022; Pekar et al, 2021). This was also demonstrated by Vivier and colleagues for NKp46‐specific Fab‐derived paratopes incorporated into multifunctional NKCEs (Gauthier et al, 2019).…”
Section: Resultsmentioning
confidence: 99%
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“…The intracytoplasmic domain has many signaling motifs, e.g. an inhibition motif based on immunoreceptor tyrosine (SaYtpL), a SH2 (Src homology 2)-binding domain (YqlQ), and a SH3-binding motif (PdaPilPvsP) ( 95 ). B7-H6 also presents a selective expression on several tumor cell types (melanoma, neuroblastoma, primary blood or bone marrow cells from various hematological malignancies, etc.…”
Section: Clinical Meanings and Functions Of B7-h6 In Gliomasmentioning
confidence: 99%