臨床婦人科産科72巻6号

2018年06月発行

今月の臨床 がん免疫療法の新展開─「知らない」ではすまない今のトレンド

がん能動免疫療法の将来展望

著者： 西村泰治¹

所属機関： ¹熊本大学大学院生命科学研究部免疫識別学分野

ページ範囲：P.592 - P.599

文献概要

●がん細胞に固有のミスセンス変異遺伝子によりコードされるネオ抗原ペプチドに対するT細胞の免疫応答，ならびに腫瘍溶解性ウイルスが腫瘍免疫に果たす役割が注目されている．

●がん免疫療法の効果は遅延して発現することが多いが，一部の患者では長期間におよぶ奏効が認められる．患者のQOLは良好であるが，自己免疫疾患などの特有の有害事象に注意する必要がある．

●がん細胞，その微小環境ならびに免疫細胞における個体差を評価するバイオマーカーを確立して，個々の患者に最適の免疫療法を選ぶことが重要である．

●がんの個体間および個体内での多様性を考慮した，免疫療法を含む多様ながん治療法の複合（併用）療法の開発が期待され，多数の治験が進行中である．

参考文献

1）Couzin-Frankel J : Breakthrough of the year 2013. Cancer immunotherapy. Science 342 : 1432─1433, 2013

2）Melief CJ, et al : Therapeutic cancer vaccines. J Clin Invest 125 : 3401─3412, 2015

3）Walter S, et al : Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med 18 : 1254─1261, 2012

4）Kono K, et al : Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens. J Transl Med 10 : 141, 2012

5）Yoshitake Y, et al : Phase II clinical trial of multiple peptide vaccination for advanced head and neck cancer patients revealed induction of immune responses and improved OS. Clin Cancer Res 21 : 312─321, 2015

6）Melief CJ, et al : Immunotherapy of established（pre）malignant disease by synthetic long peptide vaccines. Nat Rev Cancer 8 : 351─360, 2008

T cell sequestration, dysfunction and deletion. Nat Med 19 : 465─472, 2013

8）van Poelgeest MI, et al : HPV16 synthetic long peptide（HPV16-SLP） vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial. J Transl Med 11 : 88, 2013

T-cell immunity in patients with malignant tumor. Clin Cancer Res 19 : 4508─4520, 2013

10）Hirayama M, et al : An oncofetal antigen, IMP-3-derived long peptides induce immune responses of both helper T cells and CTLs. OncoImmunology 5 : e1123368, 2016

T cells expressing converged T-cell receptor genes in vitro. OncoImmunology 7 : e1415687, 2018

12）Robbins PF, et al : Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med 19 : 747─752, 2013

T cells in human melanoma. Nat Med 21 : 81─85, 2015

14）McGranahan N, et al : Allele-specific HLA loss and immune escape in lung cancer evolution. Cell 171 : 1259─1271, 2017

15）Marty R, et al : MHC-I genotype restricts the oncogenic mutational landscape. Cell 171 : 1272─1283, 2017

16）Stone JD, et al : TCR affinity for p/MHC formed by tumor antigens that are self-proteins : impact on efficacy and toxicity. Curr Opin Immunol 33 : 16─22, 2015

17）Carreno BM, et al : Cancer immunotherapy. A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science 348 : 803─808, 2015

18）Sahin U, et al : Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547 : 222─226, 2017

19）Gubin MM, et al : Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 515 : 577─581, 2014

20）Rizvi NA, et al : Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348 : 124─128, 2015

21）Sharma P, et al : The future of immune checkpoint therapy. Science 348 : 56─61, 2015

22）Chowell D, et al : Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy. Science 359 : 582─587, 2017

23）Ott PA, et al : An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 547 : 217─221, 2017

24）Kaufman HL, et al : Oncolytic viruses : a new class of immunotherapy drugs. Nat Rev Drug Discov 14 : 642─662, 2015

25）Ribas A, et al : Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy. Cell 170 : 1109─1119, 2017

26）Adam C, et al : Combination cancer therapy can confer benefit via patient-to patient variability without drug additivity or synergy. Cell 171 : 1678─1691, 2017

27）Chen DS, et al : Elements of cancer immunity and the cancer-immune set point. Nature 541 : 321─330, 2017