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Table 1 Comparison of clinical efficacy and future prospects in CAR T cell versus CAR NK cell cancer immunotherapya,b

From: Chimeric antigen receptor-engineered natural killer cells for cancer immunotherapy

Parameter CAR T Primary CAR NK CAR NK-92
Source PB PB or UCB Cell line
Need for in vitro expansion before infusion Yes Yes No
Pre-activation and differentiation Needs CD3/CD28 stimulation Requires feeder cells and/or IL-2 or other cytokines for optimal growth Requires IL-2 for optimal growth
Viral transduction efficiency Variable Variable High transduction efficiency
Side effects    
 Neurotoxicity Yes (reported in 58–87% of the patients in the Kymriah and Yescarta clinical trials) No No
 CRS Yes (reported in 74–94% of the patients in the Kymriah and Yescarta clinical trials) No No
 Long-term side effects Yes, CAR T cells can persist in circulation for years Limited in vivo survival without IL-15 and persistent growth for over a year with incorporated IL-15 Short persistence, the cell line needs to be irradiated prior to infusion
Killing activity Kills only tumor cells carrying TAA in an MHC-independent manner; produces slow response Kills tumor cells regardless of their MHC status with some preference in killing tumor cells lacking MHC-I; quick response without prior activation Similar to primary CAR NK
ADCC activity No Yes, due to CD16 expression Similar to primary CAR NK when NK-92 CAR NK cells are transduced with CD16
Prospects for clinical use Impressive clinical outcomes have already been reported; CAR T treatment has been approved by the FDA (Kymriah for ALL and Kymriah and Yescarta for DLBCL [51] Being developed and promising Being developed and combined with other agents
"Serial" killing ability Yes Yes, one NK cell can kill up to 5 tumor cells [220] Unknown because cells  are irradiated before infusion
Production efficiency Low; needs to be prepared individually for each patient and requires coordination between production facility and clinica High due to donor availability and the off-the-shelf potential High; unlimited expansion potential of the cell line
Cost of treatment Expensive; approximately $373,000 USD [221] Relatively less expensive due to off-the-shelf potential Relatively less expensive than CAR T and primary CAR NK cells due to unlimited expansion potential
Potential for production of "off-the-shelf" anti-cancer products Low to moderate; TCR knock-out studies are ongoing, but disabling TCR may lower T cell activity and/or survival and may be technically challenging High; UCB NK cells may have better survival rates than PB NK cells after thawing or infusion Very high; unlimited expansion potential
  1. a10% of the patients died or were dropped and 80% needed bridge chemotherapy while waiting for the CAR T cell product during Kymriah and Yescarta clinical trials, complicating interpretation of the results [51]. This table has been partially adopted from Kurlander (2017), O’Leary (2017) [49, 51], and Klingemann (2014) [65]
  2. bDLBCL diffuse large B-cell lymphoma, PB peripheral blood, UCB umbilical cord blood