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[The development of new BCG Immunotherapy against bladder cancer with immune checkpoint inhibitor]

Original in Japanese: The development of new BCG Immunotherapy against bladder cancer with immune checkpoint inhibitor

Funder: Japan Society for the Promotion of Science

Funding period
JPY 4.7 M
USD 42 K
Funding amount
[Superficial bladder cancer, ie muscle layer non-invasive bladder cancer (non-muscle invasive bladder Cancer is basically a transurethral resection of bladder tumor as an initial treatment (TURBT)It has been carried out. ThatTURBTThe treatment of muscular layer non-invasive bladder cancer has been significantly improved,TURBTJust not be able to completely prevent the recurrence and progress within the bladder,TURBTIn relapse prevention purposes after enforcement,BCG(bacillus Calmette-Intravesical injection therapy of Guerin) has been carried out. HoweverBCGDespite the accumulated evidence regarding the usefulness of therapy, it is often impossible to continue treatment because of its severe side effects. So in this study,BCG+抗PD-1(PD-L1) Higher antitumor effect and less side effects by using antibodyBCGIt is aiming to establish a treatment. 1. We have alreadyBCG+抗PD-1抗体がBCGResults have been shown to show stronger anti-tumor effects than monotherapy. 2. On the 28th day after the treatment, the bladder tumor was removed, treated with collagenase, and neutrophils and lymphocytes were extracted.FACSWhen it was confirmed whether neutrophils involved in the antitumor effect were effectively induced, there was no difference in the induction. OthersCD8 Tリンパ球、NKThere is no difference in the number of induction of cells etc., lymphocytes,NKIt was suggested that the nature of cells might be involved in the antitumor effect. 3. CTLActivity (cytotoxic T lymphocyte activity),NKIt was measured activity,BCG+抗PD-1抗体がBCGIt was found to show more potent activity than monotherapy, suggesting that this may be reflected in the difference in antitumor effect.]
Original in Japanese
表在性膀胱癌、すなわち筋層非浸潤性膀胱癌(non-muscle invasive bladder cancer)は、基本的に初期治療として経尿道的膀胱腫瘍 切除術(TURBT)が行われている。そのTURBTにより、筋層非浸潤性膀胱癌の治療は著しく改善されてきたが、TURBTだけでは膀胱内再発・進展を完全に防止することはできず、TURBT施行後の再発防止目的で、BCG(bacillus Calmette-Guerin)の膀胱内注入療法が行われている。しかしBCG療法の有用性に関するエビデンスが蓄積されているに関わらず、その激しい副作用故、治療継続が出来ないこと が多い。そこで本研究では、BCG+抗PD-1(PD-L1)抗体を使用し、より抗腫瘍効果の高い、またより副作用の少ないBCG治療の確立を目指している。1. 我々はすでにBCG+抗PD-1抗体がBCG単独療法よりもより強力な抗腫瘍効果を示すという結果を得ている。 2. 治療後28日目でその膀胱腫瘍を摘出しコラギナーゼ処理を施し、好中球、リンパ球を抽出。FACSにて実際に抗腫瘍効果に関与する好中球が効率的に誘導されているのかを確認したところ、その誘導に差はなかった。その他、CD8 Tリンパ球、NK細胞などもその誘導数に差はなく、リンパ球、NK細胞の性質が抗腫瘍効果に関与している可能性が示唆された。 3. CTL活性(細胞障害性Tリンパ球活性)、NK活性を測定したところ、BCG+抗PD-1抗体がBCG単独療法よりもより強力な活性を示すことが分かり、そのことが抗腫瘍効果の差に表れている可能性が示唆された。
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