作者：疑夕3 o$ L% ?* R% u0 b& `
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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 $11.38 on January 15, 2015.' C1 J! ^ B8 g) w8 i; R4 a3 ~+ K
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CAR-T cell immunotherapy has been regarded as one of the most compelling breakthroughs in cancer treatment in recent years. Companies working on CAR-T (e.g., JUNO, KITE, BLCM, BLUE, ZIOP) are red hot at present. Sorrento/Conkwest is developing CAR-expressing NK cells rather than T cells to kill cancer cells. How about CAR-TNK compares to CAR-T?; D- y6 e3 q5 u& Y( m1 Q
?; k1 y: h1 w, Q/ AHere is a comparison published in OncoImmunology[1]. The author, Hans Klingemann, is the inventor of the NK-92 cell line and co-founded ZelleRx in 2002, which was renamed Conkwest in 2010. CAR-NK has many several advantages over CAR-T:$ g# [3 f+ l2 R
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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-6.6 `' e S3 T3 G/ A% L
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(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.6 n5 n' J) C5 e$ t0 p) z
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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.* f5 e5 F# b) \9 p9 k' E! o8 j
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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. . k( j4 B) m0 J0 B 9 o' ?* N4 f4 x(5) CAR-NK cells can also be produced in large scaleunder GMP conditions. Moerover, it may be used in the setting of allogeneic transplantation.* O$ g I5 j! ?( v% S" W
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Naturally, 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. 6 U, [- u) q5 F+ r7 d+ E* [ - P' a" o" s; X- W5 j) h& I
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. : a0 o F1 A3 J ' Z& r; ?9 L6 I4 K4 ^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].. H: v h s" d" _5 c
1 M& |+ i0 l& bSorrento 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., c6 K5 h2 r7 S
' W! v- c- j) e[1] Oncoimmunology. 2014, 3, e28147. doi: 10.4161/onci.28147.% m# Q1 k9 e0 L* E* }5 ~
[2] Leukemia. 2014, 28(4), 917-927. + P7 [6 S0 |7 I) i' s ]6 d5 d 8 M6 H6 c3 a* g' x/ d4 s V( s
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What are the next generation T cell immunotherapies作者: 2357710447 时间: 2015-11-12 09:32
回复 cantonchn 的帖子. z9 p) f& P; v% r1 G% C
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有中文的么？ 英文的看起来有点难啊 作者: cneagle66 时间: 2015-11-12 21:10
本帖最后由 cneagle66 于 2015-11-12 21:15 编辑 % f8 e- m! h/ \. l % s/ B n( |& Y: Z2014年12月15日，Patrick Soon Shiong，世界上最富的医生，获得了Sorrento Therapeutic公司19.9%的股票，每股价格5.80美元，4天后，Sorrento and Conkwest 宣布共同开发CAR-NK免疫疗法，Sorrento的股票价格在2015年1月15上涨到每股11.38美元。1 f. Q; n# S' x
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CAR-T细胞免疫疗法被认为是近年来肿瘤治疗的突破性进展，很多开发CAR-T的公司（如JUNO, KITE, BLCM, BLUE, ZIOP）现在热的发红，Sorrento/Conkwest 正在研发表达CAR的NK细胞，而不是T细胞，CAR-NK和CAR-T相比如何？( O+ u1 J. D) {- f: Y; }2 C
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在OncoImmunology上有这样的比较，Hans Klingeman是NK-92细胞系的发明者，和他人在2002年共建了ZelleRx，即2010年更名为Conkwest的公司。CAR-NK具有很多优势： 8 a q, ?' j$ R1 D6 s 8 A; l" ~1 j X
（1）CAR-NK不产生IL-6，后者是细胞因子释放综合征的元凶，CAR-T治疗的临床试验所造成的多起患者死亡，都和IL-6升高有关。) X' \& ~2 J0 j. V- m4 n
* q, I6 d& N3 R7 e: x; O- F(2) CAR-NK 由于寿命较短，在外周循环中消除较快，不必担心持久的CAR相关的副反应。相应地 JUNO Therapeutics已经着手，插入EGFRt基因以控制CAR-T细胞的效应。$ X# S4 u$ Y. S7 F0 k* t
+ T3 J8 ~, A3 N9 M+ m' C! F（3）NK细胞是连环杀手，可以聪明地从一个目标移动到另一目标，杀灭7-10个细胞。 ( d' }" i/ m3 E2 [
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（4）NK-92细胞的转染效率达50%，甚至是非病毒载体也可轻易转染。不用病毒载体，就避免了癌基因的激活，插入突变等风险。+ T8 j) C3 o" `3 h6 w% Z- y
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（5）CAR-NK也可在GMP状态下批量生产，并可用于异体。 P; P1 h2 ~# E+ d
