War against Ourselves

バイオ医薬品のハードル 薬を排除する免疫

By Michael Waldholz M. ウォルドホルツ
English 日本語 日本語
Ever since he can remember, even as a boy growing up on a small farm in Michigan, Ken Martin has battled betrayal by his own body. Now 50 years old, Martin was born with hemophilia, and he bleeds almost uncontrollably from a cut. If an internal vein or artery is injured, the blood it carries pools in an intensely painful balloon under Martin’s skin. When that happens in his knees, as it frequently does, he must hobble on crutches or stay in a wheelchair until the bleeding slowly stops.  50歳のマーティン(Ken Martin)はミシガン州の小さな農園で育った少年期から記憶にある限りずっと,自分の身体による裏切り行為と闘ってきた。彼は生まれつき血友病を患っており,ちょっとした切り傷でも出血が止まらない。体内の血管が傷つくと,皮膚の下に血液がたまって風船のように膨れ,激しく痛む。よくあるようにこれが膝の内部で起こると,出血が徐々に収まるまで松葉杖か車椅子を使わねばならない。
Worse, Martin’s body has dealt him a double whammy. People have hemophilia because they lack a gene that makes an essential blood-clotting protein, and many of them get regular infusions of the missing molecule, which is called Factor VIII. But if Martin gets an injection of Factor VIII, his immune system launches a swarm of disease-fighting antibodies against the clotting protein, sweeping it away as if it were an infectious microbe. “I’ve never benefited from any regimen containing Factor VIII,” says Martin, who is married with two boys and, despite the ailment, has had a successful career as a design engineer in the auto industry. Martin deals with his bleeds by elevating and icing the swollen area and resting—and with “a lot of patience,” he says. There are about 20,000 people in the U.S. with hemophilia, and around 30 percent of those with Martin’s type experience similar antibody attacks.  さらに悪いことに,マーティンの身体は彼に二重の困難をもたらしている。血友病はある重要な血液凝固タンパク質を作る遺伝子が欠損しているために起こるので,患者の多くは「第Ⅷ因子」というそのタンパク質分子を補充する点滴を定期的に受ける。だがマーティンの場合,第Ⅷ因子を点滴すると免疫系がこの凝固タンパク質をあたかも感染性微生物のように認識し,大量の抗体を差し向けて一掃してしまう。
The problem of antidrug antibodies reaches far beyond blood-clotting disorders. ADAs, as they are called, threaten some of the newest drugs for treating cancer, heart disease and various autoimmune illnesses, such as rheumatoid arthritis. These medications, referred to as biologics, mimic naturally occurring proteins. That often makes them more effective than traditional drugs: the pills we swallow that contain small synthesized chemicals. But because our immune systems are built to detect foreign proteins, some patients react to biologics as if they were invading bacteria, and this sets off an antibody onslaught rarely seen with pills or tablets. The result is that biologic medicine can be blocked or destroyed before it can do any good.  この「抗薬物抗体(ADA)」の問題は血友病にとどまらない。がんや心臓病のほか,関節リウマチなど様々な自己免疫疾患を治療する最新の医薬品を脅かしている。バイオ医薬品(生物学的製剤)と呼ばれるそれらの薬剤は天然のタンパク質を模倣しており,小分子の合成化学物質を含む従来の飲み薬よりも効力に優れたものが多い。
Early biologic developers believed that because many of the drugs were based on human genes and proteins, the human immune system would not treat them as foreign. This turned out to be overly optimistic. When there are reactions, they are frequently big enough to ruin the drug.  初期のバイオ医薬開発者は,バイオ医薬の多くはヒトの遺伝子やタンパク質に基づいているのだから,免疫系はこれらを外来物質とは見なさないだろうと考えていた。だが,その考えは甘すぎた。免疫応答が生じた場合,薬効を台なしにするほど甚大となる例が多かった。