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 |