ENGINEERING NON-CYTOTOXIC DELIVERY OF PROTEINS BY T-CELLS VIA FUSION TO NPC2
Engineering cellular therapeutics by repurposing biological systems has great potential in immunology. The primary mechanism employed by T cells for the specific transfer of proteins at the immunological synapse is via the lysosomal perforin pathway that facilitates the transfer of cytotoxic granzymes leading to the apoptosis in target cells. Facilitating the delivery of non-cytotoxic proteins through perforin oligomers will dramatically expand the range of protein cargo that T cells can traffic to the target cells. Here, we have identified the intralysosomal protein, NPC2, as a chaperone that can facilitate the delivery of T-cell derived reporter proteins through perforin pores at the immunological synapse. By using NPC2 as a molecular chaperone, the NPC2-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies.
App Type | Case No. | Country | Patent/Publication No. | |
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Inquire | PCT | 2023-002 | PCT | WO/2024/064261 |