【转】罗氏免疫疗法MPDL3280A早期临床表现强劲

仲夏秋夜云

罗氏免疫疗法MPDL3280A早期临床表现强劲
根据提交至2013年欧洲癌症大会（ECC）的一项早期临床试验的详细数据，罗氏（Roche）开发的一种实验性免疫疗法MPDL3280A，似乎对吸烟的非小细胞肺癌（NSCLC）患者尤其有效。尽管该药还处于非常早期的开发阶段，但业界已将其定义为绝对是一个改变游戏规则（game changer）的药物。
研究数据表明，经MPDL3280A治疗的53例NSCLC患者中，23%的患者肿瘤缩小（响应率），但最令人鼓舞的是，在吸烟的NSCLC患者中，响应率为26%，而从未吸过烟的NSCLC患者中，响应率为10%。这一发现，对于NSCLC患者来说，可谓是重大消息。
肺癌，通常由吸烟引起，极难成功治愈，一旦扩散至身体其他部位，便是不治之症。
领导该项研究的科学家怀疑，与从不吸烟的肺癌患者相比，吸烟的肺癌患者肿瘤中的基因突变率较高，因此，在PD-L1被阻断时，这类患者的免疫系统可能更容易积极响应。研究团队对实验数据进行更细致地挖掘，发现这53例患者中，81%（43例）为吸烟者或曾经吸烟者，19%（10例）为不吸烟者。
该研究的领导者ean-Charles Soria在ECC上称，这是首个在吸烟者中比在非吸烟者中表现出更强活性的靶向性制剂。
MPDL3280A是一种工程化的抗体，靶向于PD-L1蛋白，这是肿瘤的一种防御机制，肿瘤能够该机制欺骗免疫系统T细胞使之失活。通过阻断PD-L1，MPDL3280A能够唤醒T细胞并识别癌细胞，随后生长的增殖来更有效地攻击癌细胞。
竞争对手默沙东（Merck & Co）和百时美施贵宝（BMS）等也在开发名为PD-1抑制剂的一类相似的免疫疗法，同样旨在调动机体自身的免疫系统，来对抗癌症。
目前，罗氏也在调查MPDL3280A用于治疗其他癌症的潜力，包括黑色素瘤和肾癌，目前该药已在这些癌症的早期试验中表现出了治疗潜力。
英文原文：Roche immunotherapy drug may be 'game changer' in lung cancer
AMSTERDAM (Reuters) - An experimental Roche drug that seems to work particularly well against lung cancer in smokers may be a "game changer" for these normally difficult-to-treat patients, researchers said on Sunday.
Presenting detailed data from an early-stage trial of the drug, called MPDL3280A, in patients with a form of the disease called non-small cell lung cancer (NSCLC), investigators said what they had found was "great news for lung cancer patients".
Of 53 patients with NSCLC tumours treated with the drug, 23 percent saw their tumours shrink, according to results presented at the European Cancer Congress (ECC) in Amsterdam.
But the most encouraging numbers were among smokers, where the response rate was 26 percent compared with 10 percent of patients who had never smoked, said Professor Jean-Charles Soria of France's Institut Gustave Roussy, who led the study.
Lung cancer, which is usually caused by smoking, is extremely difficult to treat successfully and once it has started to spread to other parts of the body, it is incurable.
Roche's MPDL3280A is an engineered antibody that targets a protein called PD-L1 - a defence mechanism that tumours use to trick the immune system's T-cells into being inactive.
By blocking PD-L1, the drug allows the T-cells to wake up and recognize the cancer, and then grow and multiply to attack it more efficiently.
Rival drugmakers including Merck and Bristol-Myers Squibb are developing immunotherapy drugs in a similar class of drugs known as PD-1 inhibitors, also designed to mobilize the body's own immune system to fight cancer.
Soria's team suspected that because lung tumours in smokers have a higher rate of genetic mutations than tumours of lung cancer patients who have never smoked, their immune systems may be more likely to respond vigorously when PD-L1 is blocked.
So they drilled down into the data more closely, separating out the 81 percent of the 53 patients who were smokers or former smokers, and the 19 percent of them who were not.
"And bingo, this is the first targeted agent (drug) that shows more activity in smokers than in non-smokers," Soria told reporters in a briefing at the ECC.
Cora Sternberg, co-chair of the ECC's scientific committee and an oncologist at the San Camillo and Forlanini hospitals in Rome who was not involved in the study, said that although the results were from very early-stage trials, they suggested the drug was "definitely a game changer" in lung cancer.
Roche is also investigating MPDL3280A's potential for treating a range of other cancers, including melanoma skin cancer and kidney cancer, where it has already shown some promise in early trials.
Cornelis van de Velde, an oncologist at Leiden University Medical Centre in the Netherlands and president of the European Cancer Organisation, said Soria's was an extremely important study for NSCLC patients, who currently have very few treatment options that make much impact on their disease.
"Hundreds of millions of euros have been spent chasing the dream of immunotherapy for lung cancer patients, but with zero results." he said. "These early findings..suggest that it has the potential to open new therapeutic approaches."

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