Multimodal targeting of metastatic renal cell carcinoma via CD70-directed allogeneic CAR-NKT cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40885188.
- Also identified by DOI 10.1016/j.xcrm.2025.102321 and PMC identifier 12490242.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Renal cell carcinoma (RCC) represents about 90% of kidney cancers, with 30%-40% of patients developing metastatic disease despite current treatments. Conventional chimeric antigen receptor (CAR)-T therapy targeting CD70 shows promise but faces challenges due to its autologous, personalized nature. Here, we develop allogeneic CD70-directed CAR-engineered invariant natural killer T (<sup>Allo</sup>CAR70-NKT) cells from hematopoietic stem and progenitor cells using a clinically guided culture method. These cells expand robustly with high purity and no fratricide risk. <sup>Allo</sup>CAR70-NKT cells exhibit potent cytotoxicity against primary and metastatic RCC via CAR- and natural killer (NK) receptor-mediated mechanisms and selectively target the immunosuppressive tumor microenvironment (TME) through T cell receptor (TCR) recognition. Additionally, they eliminate CD70<sup>+</sup> host alloreactive T cells, promoting therapeutic persistence. Taken together, our findings support the therapeutic potential of <sup>Allo</sup>CAR70-NKT cells as a next-generation, off-the-shelf immunotherapy with dual tumor- and TME-targeting functionality and the added capacity to eliminate alloreactive T cells, which offers a compelling strategy for treating metastatic RCC.
Medical subject headings
- Carcinoma, Renal Cell
- Kidney Neoplasms
- CD27 Ligand
- Receptors, Chimeric Antigen
- Immunotherapy, Adoptive
- Natural Killer T-Cells