2014年10月16日讯 /生物谷BIOON/ --最近诺华公司和美国宾夕法尼亚大学的研究团队合作开发的CAR-T疗法CTL019又添新的积极数据。在治疗儿童抗药性急性白血病的研究中，有90%的患者病情得到了缓和，而78%的患者经过治疗后生存期达到了6个月以上，可以说是成果斐然。研究人员表示目前正着手评估这种疗法的长期疗效。参与这一研究的Stephan Grupp表示，研究人员对这一疗法的疗效表示惊喜，并正在深入探讨这一疗法能够取得的最优效果。而目前接受这一疗法治疗的患者儿童最长生存期已经达到了2.5年。
CTL019的治疗主要是通过分离患者体内的T细胞并对其辅以嵌合抗原受体以提高T细胞对体内癌细胞等的识别和杀伤能力，从而特异性杀灭癌细胞。诺华公司对这一疗法寄予厚望，今年九月份就宣布投入巨资，在宾夕法尼亚州建立了相关研发基地，与宾夕法尼亚大学建立了深度的合作关系。而这一理念目前已经广泛被生物医药产业接受，一方面是FDA希望这一思路能够为癌症治疗开辟新的方向，因此在今年七月份授予这一疗法突破性药物地位，以为其研发审批提供便利。
而诺华公司绝不是唯一一个看到CAR-T前景的伯乐，目前西雅图的Juno生物医药公司以及Kite生物医药公司和BlueBird生物医药公司都在这一领域进行着自己的研究。可以预见，在不久的未来，癌症治疗领域或将出现一股CAR-T疗法的高潮。
详细英文报道：
Investigators working on Novartis' ($NVS) personalized CTL019 CAR-T program at the University of Pennsylvaniasay that 90% of a small group of children suffering from very advanced cases of treatment-resistant acute lymphoblastic leukemia achieved complete remission in the newly updated trial. With 78% of these kids alive 6 months after treatment, the physicians in charge say they're beginning to track some long-lasting results that underscore the therapeutic potential for this therapy, which is now in Phase II and may be ready for regulators as early as 2016.
"We have been amazed how well that has been working," says Stephan Grupp, a professor of pediatrics in Penn's Perelman School of Medicine.
The Novartis-backed effort turned early to the pediatric population, and now Grupp says that investigators are able to report some long-term effects, with one child being treated for 2.5 years.
"That's a first," says Grupp, adding that these responses in a clinical trial are "unprecedented."
CTL019 is a new therapy that is made by extracting T cells from patients and arming them with chimeric antigen receptors, which essentially trains the immune system's foot soldiers to track down and kill tumor cells. Novartis has been financing an ambitious effort to accelerate these treatments as fast as possible in the hope of gaining some quick approvals for what promises to be a revolutionary advance in cancer therapy.
The FDA has also provided "breakthrough" status for the treatment, which should help shorten the amount of time it will take to gain an approval.
In addition to the effort at Penn, Juno in Seattle and other players like Kite ($KITE) and bluebird ($BLUE) have been ramping up their own efforts. But CAR-T treatments aren't without risk. Eight of the children in this study experienced a cytokine storm that was so severe they had to be hospitalized. But they all recovered.
"Everybody gets some kind of CRS" reaction, says Grupp, and a third of them end up in the ICU with serious reactions. But investigators have also learned that by blocking IL-6 with the immunosuppressant tocilizumab, they can often prevent the worst reactions. Another key lesson emerging from the study: The toxicity reflected in the data is directly linked to the disease burden. The lower the disease burden, the lower the odds for a serious reaction, which bodes well for patients once the treatment is used in less advanced patient groups.
The next step, says Grupp, is to focus on the Phase II study, which includes 8 or 9 centers around the country. "We have to show that other centers can do this," he says. And then Novartis says it could be able to file for an approval around the 2016 time frame.
The research group says it now has a half-dozen other CAR trials open, including a newly launched glioblastoma study targeting EGFR, and the multicenter ALL trials--for both pediatric patients and adults--are on track to open this fall. Plans are also now set for the construction of the Penn-Novartis Center for Advanced Cellular Therapeutics, a $20 million facility being funded by Novartis.