Summary of theโ Research on Engineered CAR-NK Cells:
This research focuses on improving CAR-NK cell โtherapy – a promisingโฃ cancer treatment – by overcoming a keyโ obstacle: โฃ immuneโ rejection of donor NK cells. Hear’s a breakdown โofโ the โkey โขpoints:
*โ the Problem: CAR-NK cells, engineeredโ to โtarget and โdestroy cancerโ cells,โ can be derived from healthy โdonors forโ faster, massโ production. However, the recipient’s immune system โoften โคrecognizes and destroys these donor cells before they can fight the cancer.
* The Solution: MIT researchers engineered NK cells to “hide” from โคthe immune system by removing HLA class 1 proteins – โtheโ identity markers that signal “foreign” to the immuneโ system. They achieved this using siRNA to silence โthe genes โresponsible for producing these proteins.
* Enhancements: โค alongside removing HLA class 1,they also added genes โขfor PD-L1 or SCE to boost theโ NK โcells’ cancer-fightingโค ability and the CAR gene to target specific cancer cells (CD-19 in this study).All theseโ components were combined into a single DNA construct for efficient โคengineering.
* Results in Mice: Mice with human-like immune systems and lymphoma were used โคto test the engineered cells.
โค โ โฃ*โฃ Mice receiving the modified CAR-NK cells โฃshowed long-lasting NK cell populations (at least 3 weeks) and significant cancer elimination.
โ*โค Control groups (unmodified NK cells orโ CAR-NK โcells without HLAโ class 1 removal) experienced immune rejection of the donor NK โcells, โcancer progression, and cell death within 2 weeks.
โ โข * The engineered cells also showed a reduced risk of cytokine release syndrome, aโ dangerous side effect of immunotherapy.
* โค Future Directions:
* Clinical trials are planned in collaboration withโข Dana-Farber.
โฃ * โขTesting the therapy for โฃ lupus, an autoimmune disorder, is โขunderway with a biotech company.
โ โค* The researchers believe this construct can โbe adapted โขto existing CAR-NKโค cell therapies targetingโ different cancers.
In essence, this researchโค represents a significant step towards โฃmaking donor-derived โCAR-NK cell therapy a viable and perhaps safer choiceโ to CAR-T cell therapy.