A pilot study on the safety and efficacy of neoadjuvant chemo‑adoptive immunotherapy for locally advanced rectal cancer

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

doi:10.3892/ol.2024.14234

A pilot study on the safety and efficacy of neoadjuvant chemo‑adoptive immunotherapy for locally advanced rectal cancer

Authors:
- Yu Okazawa
- Takashi Kamigaki
- Kiichi Sugimoto
- Takeshi Yamada
- Yoichiro Yoshida
- Sachiko Okada
- Hiroshi Ibe
- Eri Oguma
- Takuma Iwai
- Akihisa Matsuda
- Teppei Yamada
- Suguru Hasegawa
- Shigenori Goto
- Rishu Takimoto
- Kazuhiro Sakamoto
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Affiliations: 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, Department of Gastrointestinal and Hepato‑Biliary‑Pancreatic Surgery, Nippon Medical School, Tokyo 113‑8603, Japan, Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka 814‑0180, Japan
Published online on: January 15, 2024 https://doi.org/10.3892/ol.2024.14234
Article Number: 101
Copyright: © Okazawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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).

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