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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 $11.38 on January 15, 2015. 8 `( A# d3 W% n4 x: c7 u7 W 9 R& m3 {$ X2 O: R% X8 zCAR-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?3 T/ a* n6 S( F1 t
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Here 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:" A& l3 y( a! _( q4 |7 |/ E
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(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. ) [ N2 c* \& q* Z# w# n) H# t) f( _ 4 T9 y! z- _: n* y) ?+ b
(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.' F* }5 T+ E7 O4 g( L, V: @
" V/ n) G1 z5 x(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.% L' y& C) j1 A
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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.& b& r% z) ? p: y" _) }
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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. 0 h" f+ A, M8 {9 V7 }/ B E$ y! q' A! B7 ]0 U8 VNaturally, 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.# C: `2 b1 Z9 ?! \( f
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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. 1 U5 a" |2 k, i! t + e8 y" M) w- ?
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].' ~# l8 N3 ]/ u; k& g' J
8 o" [% A/ M6 j9 r- x- W# ?2 @( R# RSorrento intends to develop anti-CD19, anti-PDL1, anti-PSMA, and anti-CD123 CAR-NK cells. It is expected to initiate Phase I trials in 2016.3 s& F8 h ?; c8 H# O
4 v, C' ^9 p4 a( J8 W H( b[1] Oncoimmunology. 2014, 3, e28147. doi: 10.4161/onci.28147. " _- e3 C, u3 T: `8 q1 y[2] Leukemia. 2014, 28(4), 917-927. 6 D9 i% K; R \. B3 q# k
5 g' ~" J! @) B* X# K/ p* MRelated Articles: 9 Y1 d0 [8 `7 J4 gWhat are the next generation T cell immunotherapies作者: 2357710447 时间: 2015-11-12 09:32
