Nanobody-based CAR NK cells for possible immunotherapy of MICA tumors.
(2024) PNAS nexus — Vol. 3, n° 5, p. pgae184 (2024)
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- Authors
Verhaar, Elisha R 
van Keizerswaard, Willemijn J C Knoflook, Anouk Balligand, Thomas Ploegh, Hidde L
- Abstract
- The glycoproteins MICA and MICB are upregulated on the surface of cells undergoing stress, for instance due to (viral) infection or malignant transformation. MICA/B are the ligands for the activating receptor NKG2D, found on cytotoxic immune cells like NK cells, CD8 T cells, and γδ T cells. Upon engagement of NKG2D, these cells are activated to eradicate the MICA/B-positive targets, assisted by the secretion of cytokines. Nanobodies, or VHHs, are derived from the variable regions of camelid heavy-chain only immunoglobulins. Nanobodies are characterized by their small size, ease of production, stability, and specificity of recognition. We generated nanobodies that recognize membrane-bound MICA with high affinity. Here, we use these nanobodies as building blocks for a chimeric antigen receptor (CAR) to establish VHH-based CAR NK cells. These anti-MICA nanobody-based CAR NK cells recognize and selectively kill MICA-positive tumor cells in vitro and in vivo. We track localization of the VHH-based CAR NK cells to MICA-positive lung metastases by immuno-positron emission tomography imaging.
- Affiliations
PCMM, Boston Children's Hospital - Harvard Medical School
Citations
Verhaar, E. R., van Keizerswaard, W. J. C., Knoflook, A., Balligand, T., & Ploegh, H. L. (2024). Nanobody-based CAR NK cells for possible immunotherapy of MICA tumors. PNAS nexus, 3(5), pgae184. https://doi.org/10.1093/pnasnexus/pgae184 (Original work published 2024)