Natural Killer Cell-based Therapies, Day 61

Natural killer (NK) cells are 𝘪𝘯𝘯𝘢𝘵𝘦 𝘭𝘺𝘮𝘱𝘩𝘰𝘤𝘺𝘵𝘦𝘴 capable of recognizing and eliminating tumor and virally infected cells without prior sensitization [1]. NK-based immunotherapies are emerging as promising alternatives to conventional T cell approaches due to their potent cytotoxicity and reduced risk of graft-versus-host disease (GvHD) [2]. 

𝘊𝘈𝘙-𝘕𝘒 𝘤𝘦𝘭𝘭𝘴 combine the specificity of chimeric antigen receptors with the natural cytotoxicity of NK cells. Unlike CAR-T cells, CAR-NK therapies may 𝘣𝘦𝘵𝘵𝘦𝘳 𝘪𝘯𝘧𝘪𝘭𝘵𝘳𝘢𝘵𝘦 𝘴𝘰𝘭𝘪𝘥 𝘵𝘶𝘮𝘰𝘳𝘴 𝘢𝘯𝘥 𝘱𝘦𝘳𝘴𝘪𝘴𝘵 𝘪𝘯 𝘪𝘮𝘮𝘶𝘯𝘰𝘴𝘶𝘱𝘱𝘳𝘦𝘴𝘴𝘪𝘷𝘦 𝘵𝘶𝘮𝘰𝘳 𝘮𝘪𝘤𝘳𝘰𝘦𝘯𝘷𝘪𝘳𝘰𝘯𝘮𝘦𝘯𝘵𝘴 (𝘛𝘔𝘌) 𝘸𝘩𝘪𝘭𝘦 𝘮𝘪𝘯𝘪𝘮𝘪𝘻𝘪𝘯𝘨 𝘴𝘦𝘷𝘦𝘳𝘦 𝘤𝘺𝘵𝘰𝘬𝘪𝘯𝘦 𝘳𝘦𝘭𝘦𝘢𝘴𝘦 𝘴𝘺𝘯𝘥𝘳𝘰𝘮𝘦 [3]. Other NK-based approaches include expanded allogeneic NK infusions, NK cell engagers, and memory-like NK cells, which aim to enhance cytotoxicity and persistence in vivo [4].  

NK therapies hold promise in solid tumor immunotherapy, as their ability to navigate dense TMEs and resist exhaustion may overcome key limitations faced by CAR-T therapies [5]. 

𝗦𝗽𝗲𝗰𝘂𝗹𝗮𝘁𝗶𝘃𝗲 𝗵𝘆𝗽𝗼𝘁𝗵𝗲𝘀𝗶𝘀:  
Combining CAR-NK therapy with checkpoint blockade or local cytokine delivery (e.g., IL-15) could further enhance NK infiltration and cytotoxicity in ´cold´ solid tumors, potentially establishing a bridge between innate and adaptive anti-tumor immunity. 

𝗤𝘂𝗲𝘀𝘁𝗶𝗼𝗻 𝗳𝗼𝗿 𝘁𝗵𝗲 𝗮𝘂𝗱𝗶𝗲𝗻𝗰𝗲:   What tumor types do you think would most benefit from CAR-NK therapy, and why? 

Stay tuned for 𝗗𝗮𝘆 𝟲𝟮: 𝗥𝗲𝗽𝗿𝗼𝗴𝗿𝗮𝗺𝗺𝗶𝗻𝗴 𝘁𝗵𝗲 𝗗𝗲𝗳𝗲𝗻𝗱𝗲𝗿𝘀 – 𝗠𝗮𝗰𝗿𝗼𝗽𝗵𝗮𝗴𝗲-𝗕𝗮𝘀𝗲𝗱 𝗖𝗲𝗹𝗹 𝗧𝗵𝗲𝗿𝗮𝗽𝗶𝗲𝘀 

𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀: 
1. DOI: 10.1038/s41577-018-0061-z 
2. doi: 10.3389/fimmu.2015.00578 
3. DOI: 10.1056/NEJMoa1910607 
4. https://doi.org/10.1007/s40291-021-00550-6 
5. DOI: 10.3389/fimmu.2025.1603757 

#Immunology #NKCells #CART #Immunotherapy #CancerResearch #SolidTumors #CellTherapy #NextGenImmunotherapy #TumorMicroenvironment #AdoptiveCellTherapy