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作者：疑夕: i; Z( g* }3 T5 ?4 o
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On December 15, 2014, Patrick Soon Shiong, the richest physician in the world, acquired 19.9% of Sorrento Therapeutics (NASDAQ: SRNE)’s equity at $5.80 per share (about 41.7 million). Four days later, Sorrento and Conkwest announced an agreement to co-develop CAR-NK immunotherapy. Sorrento’s stock price reached a high of $11.38 on January 15, 2015.
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" S4 J" x9 Z% N" T; VCAR-T cell immunotherapy has been regarded as one of the most compelling breakthroughs in cancer treatment in recent years. Companies working on CAR-T (e.g., JUNO, KITE, BLCM, BLUE, ZIOP) are red hot at present. Sorrento/Conkwest is developing CAR-expressing NK cells rather than T cells to kill cancer cells. How about CAR-TNK compares to CAR-T?0 R8 h3 [; m; F. O
. f: J. W& U/ k9 c3 R- N" GHere is a comparison published in OncoImmunology[1]. The author, Hans Klingemann, is the inventor of the NK-92 cell line and co-founded ZelleRx in 2002, which was renamed Conkwest in 2010. CAR-NK has many several advantages over CAR-T:
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/ C& `' e6 W6 v1 K/ K! D7 o. c(1) CAR-NK cells don’t produce IL-6 which is associated with the cytokine release syndrome. A series of patient deaths in the trials of CAR-T were linked to unusually high levels of IL-6." Q9 P8 E; A5 y4 j" s! ^
8 V, R; k4 T1 U+ x(2) CAR-NK cells disappear relatively rapidly from the circulation owing to their limited lifespan. There is no concern about persisting CAR-associated side effects. Whereas Juno Therapeutics has to insert EGFRt gene into the CAR-T cells to control them.
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(3) NK cells are known as serial killers which diligently moves from one target to the next one, killing on as many as 7-10 cells.; r% v1 [) L" A5 h
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(4) The transfection efficiency of NK-92 cells is about 50%, even with non-viral methods. Avoiding viral vectors eliminates the risks of oncogene activation and insertional mutagenesis.
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(5) CAR-NK cells can also be produced in large scaleunder GMP conditions. Moerover, it may be used in the setting of allogeneic transplantation.
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1 O, J6 m8 z. o8 {$ H# ONaturally, only about 10% of circulating lymphocytes are NK cells. The activation of NK cells is determined by the balance of inhibitory and activating receptor stimulation. MHC class I molecules in normal cells inhibit the activation of NK cells.8 n3 W3 I+ A# e5 O u, v
; b9 G: w; b; \Natural NK cells do not express antigen specific receptors. Can CAR-NK cells equipped with an antigen specific receptor kill cancer cells as effectively as CAR-T cells? Hard to say./ z) q9 Y3 j' X4 u- ^& H
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Preclinical studies in leukemia, lymphoma, and multiple myeloma have been reported. For instance, treatment with anti-CS1 CAR-NK cells prolonged the survival of multiple myeloma mice from 40 days to 50 days[2]." _7 m1 C) v) a! s- |5 b% ?
: B0 E2 E5 J$ _6 xSorrento intends to develop anti-CD19, anti-PDL1, anti-PSMA, and anti-CD123 CAR-NK cells. It is expected to initiate Phase I trials in 2016.! ^" |$ g% O5 r z, ]
. k) y7 i1 h! s( h" b5 d8 s[1] Oncoimmunology. 2014, 3, e28147. doi: 10.4161/onci.28147.9 C6 p% P7 Q _, _2 X7 k! E
[2] Leukemia. 2014, 28(4), 917-927. 4 j4 f! C+ a& v# H0 j$ Y
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发表于 2015-11-11 10:59
