急性リンパ性白血病に対するCAR-T細胞療法
悪性腫瘍に対する免疫療法の歴史は古いが，ほとんどの場合その効果は限定的で治療の中心にはなり得なかった。chimeric antigen receptor-T（CAR-T）細胞は，主として抗体の可変部位とT細胞受容体の細胞内ドメインからなるキメラ抗原受容体をT細胞に強制発現させた細胞で，抗原提示細胞の介在を必要とすることなく，抗体由来の抗原特異性で活性化される。初期の臨床試験では目立った効果が得られなかったものの，CD19を標的とした第2世代CAR-T細胞療法は，再発/難治の急性リンパ性白血病に対して優れた効果を発揮することが示された。一方で重篤なサイトカイン放出症候群（cytokine rel...
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| Published in | 日本造血細胞移植学会雑誌 Vol. 9; no. 4; pp. 93 - 99 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本造血細胞移植学会
2020
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| Subjects | |
| Online Access | Get full text |
| ISSN | 2186-5612 |
| DOI | 10.7889/hct-20-004 |
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| Abstract | 悪性腫瘍に対する免疫療法の歴史は古いが，ほとんどの場合その効果は限定的で治療の中心にはなり得なかった。chimeric antigen receptor-T（CAR-T）細胞は，主として抗体の可変部位とT細胞受容体の細胞内ドメインからなるキメラ抗原受容体をT細胞に強制発現させた細胞で，抗原提示細胞の介在を必要とすることなく，抗体由来の抗原特異性で活性化される。初期の臨床試験では目立った効果が得られなかったものの，CD19を標的とした第2世代CAR-T細胞療法は，再発/難治の急性リンパ性白血病に対して優れた効果を発揮することが示された。一方で重篤なサイトカイン放出症候群（cytokine release syndrome，CRS）や神経症状の合併など，安全性に関して克服すべき問題点も多い。本稿ではCAR-T細胞の開発の経緯と臨床応用の現状，さらには今後について概説した。 |
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| AbstractList | 悪性腫瘍に対する免疫療法の歴史は古いが，ほとんどの場合その効果は限定的で治療の中心にはなり得なかった。chimeric antigen receptor-T（CAR-T）細胞は，主として抗体の可変部位とT細胞受容体の細胞内ドメインからなるキメラ抗原受容体をT細胞に強制発現させた細胞で，抗原提示細胞の介在を必要とすることなく，抗体由来の抗原特異性で活性化される。初期の臨床試験では目立った効果が得られなかったものの，CD19を標的とした第2世代CAR-T細胞療法は，再発/難治の急性リンパ性白血病に対して優れた効果を発揮することが示された。一方で重篤なサイトカイン放出症候群（cytokine release syndrome，CRS）や神経症状の合併など，安全性に関して克服すべき問題点も多い。本稿ではCAR-T細胞の開発の経緯と臨床応用の現状，さらには今後について概説した。 |
| Author | 加藤, 格 梅田, 雄嗣 平松, 英文 滝田, 順子 足立, 壯一 |
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| References | 3. Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2015; 373: 1541-1552. 14. Norelli M, Camisa B, Barbiera G, et al. Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nat Med. 2018; 24: 739-748. 22. Qasim W, Zhan H, Samarasinghe S, et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017; 9: eaaj2013. doi: 10.1126/scitranslmed.aaj2013. 20. Sotillo E, Barrett DM, Black KL, et al. Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy. Cancer Discov. 2015; 5: 1282-1295. 13. Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014; 371: 1507-1517. 8. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989; 86: 10024-10028. 6. Coley WB. The Treatment of Inoperable Sarcoma by Bacterial Toxins. Practitioner. 1909; 83: 589-613. 12. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016; 127: 3321-3330. 17. Davila ML, Riviere I, Wang X, et al. Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Sci Transl Med. 2014; 6: 224ra25. 15. Gust J, Hay KA, Hanafi LA, et al. Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells. Cancer Discov. 2017; 7: 1404-1419. 1. Horibe K, Saito AM, Takimoto T, et al. Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006-2010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol. 2013; 98: 74-88. 19. Zhou X, Dotti G, Krance RA, et al. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015; 125: 4103-4113. 2. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006; 354: 166-178. 5. Tallen G, Ratei R, Mann G, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010; 28: 2339-2347. 21. Fry TJ, Shah NN, Orentas RJ, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018; 24: 20-28. 18. Paszkiewicz PJ, Fräßle SP, Srivastava S, et al. Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia. J Clin Invest. 2016; 126: 4262-4272. 16. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014; 124: 188-195. 4. Einsiedel HG, von Stackelberg A, Hartmann R, et al. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87. J Clin Oncol. 2005; 23: 7942-7950. 7. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013; 368: 1509-1518. 10. Lamers CHJ, Sleijfer S, Vulto AG, et al. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol. 2006; 24: e20-e22. 11. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018; 378: 439-448. 9. Kershaw MH, Westwood JA, Parker LL, et al. A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer. Clinical Cancer Research. 2006; 12: 6106-6115. |
| References_xml | – reference: 5. Tallen G, Ratei R, Mann G, et al. Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90. J Clin Oncol. 2010; 28: 2339-2347. – reference: 8. Gross G, Waks T, Eshhar Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A. 1989; 86: 10024-10028. – reference: 14. Norelli M, Camisa B, Barbiera G, et al. Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nat Med. 2018; 24: 739-748. – reference: 12. Brudno JN, Kochenderfer JN. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood. 2016; 127: 3321-3330. – reference: 21. Fry TJ, Shah NN, Orentas RJ, et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018; 24: 20-28. – reference: 9. Kershaw MH, Westwood JA, Parker LL, et al. A Phase I Study on Adoptive Immunotherapy Using Gene-Modified T Cells for Ovarian Cancer. Clinical Cancer Research. 2006; 12: 6106-6115. – reference: 6. Coley WB. The Treatment of Inoperable Sarcoma by Bacterial Toxins. Practitioner. 1909; 83: 589-613. – reference: 17. Davila ML, Riviere I, Wang X, et al. Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Sci Transl Med. 2014; 6: 224ra25. – reference: 2. Pui CH, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006; 354: 166-178. – reference: 18. Paszkiewicz PJ, Fräßle SP, Srivastava S, et al. Targeted antibody-mediated depletion of murine CD19 CAR T cells permanently reverses B cell aplasia. J Clin Invest. 2016; 126: 4262-4272. – reference: 19. Zhou X, Dotti G, Krance RA, et al. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015; 125: 4103-4113. – reference: 7. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013; 368: 1509-1518. – reference: 15. Gust J, Hay KA, Hanafi LA, et al. Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells. Cancer Discov. 2017; 7: 1404-1419. – reference: 1. Horibe K, Saito AM, Takimoto T, et al. Incidence and survival rates of hematological malignancies in Japanese children and adolescents (2006-2010): based on registry data from the Japanese Society of Pediatric Hematology. Int J Hematol. 2013; 98: 74-88. – reference: 11. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018; 378: 439-448. – reference: 3. Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2015; 373: 1541-1552. – reference: 4. Einsiedel HG, von Stackelberg A, Hartmann R, et al. Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Münster Group 87. J Clin Oncol. 2005; 23: 7942-7950. – reference: 10. Lamers CHJ, Sleijfer S, Vulto AG, et al. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol. 2006; 24: e20-e22. – reference: 16. Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014; 124: 188-195. – reference: 20. Sotillo E, Barrett DM, Black KL, et al. Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy. Cancer Discov. 2015; 5: 1282-1295. – reference: 13. Maude SL, Frey N, Shaw PA, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014; 371: 1507-1517. – reference: 22. Qasim W, Zhan H, Samarasinghe S, et al. Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med. 2017; 9: eaaj2013. doi: 10.1126/scitranslmed.aaj2013. |
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| Snippet | 悪性腫瘍に対する免疫療法の歴史は古いが，ほとんどの場合その効果は限定的で治療の中心にはなり得なかった。chimeric antigen receptor-T（CAR-T）細胞は，主として抗体の... |
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| SubjectTerms | cancer immunotherapy CAR-T relapsed/refractory ALL |
| Title | 急性リンパ性白血病に対するCAR-T細胞療法 |
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