Okazawa Yu, Kamigaki Takashi, Sugimoto Kiichi, Yamada Takeshi, Yoshida Yoichiro, Okada Sachiko, Ibe Hiroshi, Oguma Eri, Iwai Takuma, Matsuda Akihisa, Yamada Teppei, Hasegawa Suguru, Goto Shigenori, Takimoto Rishu, Sakamoto Kazuhiro
Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University, Tokyo 113-8421, Japan.
Department of Next-Generation Cell and Immune Therapy, Faculty of Medicine, Juntendo University, Tokyo 113-8421, Japan.
Oncol Lett. 2024 Jan 15;27(3):101. doi: 10.3892/ol.2024.14234. eCollection 2024 Mar.
The safety and efficacy of combination therapy of immune cell therapy and chemotherapy [chemo-adoptive immunotherapy (CAIT)] for patients with stage IV or recurrent colorectal cancer have been reported. In the present study, the safety and efficacy of neoadjuvant CAIT were investigated for preoperative therapy of locally advanced rectal cancer. The study included patients with cT3/T4 or cN (+) rectal adenocarcinoma scheduled for curative surgery. Six patients who consented to participate in the current study were selected as subjects. Neoadjuvant CAIT involves administration of activated autologous lymphocytes, αβ T cells, and mFOLFOX6 every 2 weeks for six courses, followed by surgery 4-6 weeks thereafter. Common Terminology Criteria for Adverse Events grade 3 neutropenia was observed in one patient. Neoadjuvant CAIT and curative surgery were performed on all the patients. The confirmed response rate was 67%. Downstaging was confirmed in five patients (83%). Regarding histological effects, two patients were grade 1a and four were grade 2. Regarding immunological reactions, both CD4 and CD8 T cell infiltration rates increased after treatment in three patients on tumor-infiltrating lymphocyte (TIL) analysis. In peripheral blood analysis, the total lymphocyte count was maintained in all patients, and the CD8 T cell count increased by ≥3 times on the pretreatment count in two patients but may not be associated with changes in TILs. During the median postoperative follow-up duration of 24 months, liver and lung metastases occurred in one patient, but all patients survived. In conclusion, neoadjuvant CAIT (αβ T cells + mFOLFOX6) can be safely administered for the treatment of advanced rectal cancer. Verification of the efficacy of comprehensive immune cell therapy, especially the induction of antitumor immunity for the prevention of recurrence, will be maintained. The current study is registered with the Japan Registry of Clinical Trials (jRCT; ID, jRCTc030190248; January 21, 2019).
免疫细胞疗法与化疗联合治疗（化疗辅助免疫疗法，CAIT）用于IV期或复发性结直肠癌患者的安全性和有效性已有报道。在本研究中，对新辅助CAIT用于局部晚期直肠癌术前治疗的安全性和有效性进行了调查。该研究纳入了计划进行根治性手术的cT3/T4或cN（+）直肠腺癌患者。选择了6名同意参与本研究的患者作为研究对象。新辅助CAIT包括每2周给予活化的自体淋巴细胞、αβ T细胞和mFOLFOX6，共六个疗程，之后4-6周进行手术。1例患者出现了不良事件通用术语标准3级中性粒细胞减少。所有患者均接受了新辅助CAIT和根治性手术。确认的缓解率为67%。5例患者（83%）确认肿瘤降期。在组织学效果方面，2例患者为1a级，4例为2级。在免疫反应方面，对3例患者进行肿瘤浸润淋巴细胞（TIL）分析，治疗后CD4和CD8 T细胞浸润率均增加。在外周血分析中，所有患者的总淋巴细胞计数均得以维持，2例患者的CD8 T细胞计数较治疗前计数增加了≥3倍，但这可能与TILs的变化无关。在术后中位随访期24个月期间，1例患者发生肝转移和肺转移，但所有患者均存活。总之，新辅助CAIT（αβ T细胞+mFOLFOX6）可安全用于晚期直肠癌的治疗。全面免疫细胞疗法的疗效验证，尤其是诱导抗肿瘤免疫以预防复发，将继续进行。本研究已在日本临床试验注册中心注册（jRCT；ID，jRCTc030190248；2019年1月21日）。
