内容紹介
Local Injection of BRM-Activated Killer Cells into an Abdominal Wall Tumor
Summary
Based on the concept of living with cancer, wherein the goal is to help patients with highly advanced solid cancers maintain a high quality of life(QOL)without adverse events and drug resistance, we developed a new immunocyte therapy based on BRM-activated killer(BAK)cells, which are primarily CD56 positive lymphocytes. In a previous report, we documented the disappearance of liver metastases, as assessed by positron emission tomography-computed tomography(PET-CT), in patients with metastatic liver cancers into which BAK immunocytes had been administered via injection into the hepatic artery. Herein, upon the patient's request, we locally injected BAK lymphocytes into an abdominal tumor. In BAK therapy, 20 mL of peripheral blood are collected from a patient. Lymphocytes from this blood sample are subsequently activated and multiplied with immobilized anti-CD3 antibodies and IL-2 and are cultured for 2 weeks with E(bina)and serum-free ALys media to yield approximately 10 billion autologous lymphocytes. On the final day of incubation, the lymphocytes are treated with 1,000 units/mL of interferon(IFN)-α for 15 minutes to enhance their therapeutic killing effects. During the second week, approximately 10 billion isolated autologous lymphocytes are suspended in 200 mL of Ringer's solution and are then drip-infused into the patient over a period of 1 hour. We injected approximately 10 billion BAK lymphocytes suspended in 50 mL of Ringer's solution into a 2-cm abdominal tumor in a single 60-year-old woman under ultrasonography guidance. This procedure was repeated every 3 weeks. After the third administration, we collected a biopsy specimen and examined it using PAS staining and microscopy. The 3 separate local injections of approximately 10 billion activated autologous lymphocytes each, primarily CD56 positive cells, into the tumor led to tumor fragmentation, leaving approximately 10 lymphocytes surrounding each cancer cell. These results suggest that BAK therapy is efficacious and show that locally administered BAK lymphocytes can reach cancer tissues and effectively kill cancer cells.
要旨
われわれは,高度進行固形癌に対して副作用がなく,耐性もできず,QOLを良好に維持しながら“がんと共生しよう”という発想の下,CD56陽性リンパ球を中心とした新免疫細胞BAK(BRM activated killer)療法を考案した。前報にて,肝動注による転移性肝癌への治療を行い,肝転移PET-CT画像の消失を報告した。今回は,患者の希望により腹壁腫瘍へのBAKリンパ球の局注療法を試みた。BAK療法とは,患者から末梢血20 mLを採取し,リンパ球を固相化CD3抗体とIL-2で活性化,増殖させ,E(bina)培地と無血清ALyS培地で2週間培養し,100億個の自己リンパ球を得る。培養最終日にIFN-αを1,000単位/mL,15分間処理しキラー活性を増強させる。2週間目に100億個の自己リンパ球だけを200 mLのリンゲル液に入れ,1時間かけて点滴静注で患者に戻す方法である。60歳,女性の2 cm大の腹壁腫瘍に100億個のBAKリンパ球を50 mLのリンゲル液に入れ,3週間ごと3回超音波検査下腫瘍内投与を行った。3回投与終了後に生検を行い,PAS染色により鏡検した。その結果,腫瘍はばらばらになり,1個の癌細胞を10個のリンパ球が取り囲んで殺している像をとらえることができた。すなわちBAKリンパ球の局注療法は,BAKリンパ球が癌組織に到達することができれば確実に癌細胞を殺していることを確かめたことになり,BAK療法の有効性が示唆された。
目次
Summary
Based on the concept of living with cancer, wherein the goal is to help patients with highly advanced solid cancers maintain a high quality of life(QOL)without adverse events and drug resistance, we developed a new immunocyte therapy based on BRM-activated killer(BAK)cells, which are primarily CD56 positive lymphocytes. In a previous report, we documented the disappearance of liver metastases, as assessed by positron emission tomography-computed tomography(PET-CT), in patients with metastatic liver cancers into which BAK immunocytes had been administered via injection into the hepatic artery. Herein, upon the patient's request, we locally injected BAK lymphocytes into an abdominal tumor. In BAK therapy, 20 mL of peripheral blood are collected from a patient. Lymphocytes from this blood sample are subsequently activated and multiplied with immobilized anti-CD3 antibodies and IL-2 and are cultured for 2 weeks with E(bina)and serum-free ALys media to yield approximately 10 billion autologous lymphocytes. On the final day of incubation, the lymphocytes are treated with 1,000 units/mL of interferon(IFN)-α for 15 minutes to enhance their therapeutic killing effects. During the second week, approximately 10 billion isolated autologous lymphocytes are suspended in 200 mL of Ringer's solution and are then drip-infused into the patient over a period of 1 hour. We injected approximately 10 billion BAK lymphocytes suspended in 50 mL of Ringer's solution into a 2-cm abdominal tumor in a single 60-year-old woman under ultrasonography guidance. This procedure was repeated every 3 weeks. After the third administration, we collected a biopsy specimen and examined it using PAS staining and microscopy. The 3 separate local injections of approximately 10 billion activated autologous lymphocytes each, primarily CD56 positive cells, into the tumor led to tumor fragmentation, leaving approximately 10 lymphocytes surrounding each cancer cell. These results suggest that BAK therapy is efficacious and show that locally administered BAK lymphocytes can reach cancer tissues and effectively kill cancer cells.
要旨
われわれは,高度進行固形癌に対して副作用がなく,耐性もできず,QOLを良好に維持しながら“がんと共生しよう”という発想の下,CD56陽性リンパ球を中心とした新免疫細胞BAK(BRM activated killer)療法を考案した。前報にて,肝動注による転移性肝癌への治療を行い,肝転移PET-CT画像の消失を報告した。今回は,患者の希望により腹壁腫瘍へのBAKリンパ球の局注療法を試みた。BAK療法とは,患者から末梢血20 mLを採取し,リンパ球を固相化CD3抗体とIL-2で活性化,増殖させ,E(bina)培地と無血清ALyS培地で2週間培養し,100億個の自己リンパ球を得る。培養最終日にIFN-αを1,000単位/mL,15分間処理しキラー活性を増強させる。2週間目に100億個の自己リンパ球だけを200 mLのリンゲル液に入れ,1時間かけて点滴静注で患者に戻す方法である。60歳,女性の2 cm大の腹壁腫瘍に100億個のBAKリンパ球を50 mLのリンゲル液に入れ,3週間ごと3回超音波検査下腫瘍内投与を行った。3回投与終了後に生検を行い,PAS染色により鏡検した。その結果,腫瘍はばらばらになり,1個の癌細胞を10個のリンパ球が取り囲んで殺している像をとらえることができた。すなわちBAKリンパ球の局注療法は,BAKリンパ球が癌組織に到達することができれば確実に癌細胞を殺していることを確かめたことになり,BAK療法の有効性が示唆された。