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Comprehensive immunological analyses of colorectal cancer patients in the phase I/II study of quickly matured dendritic cell vaccine pulsed with carcinoembryonic antigen peptide

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Abstract

Dendritic cell (DC) vaccine has been used to treat patients with advanced colorectal cancer (CRC). The results of vaccine-induced clinical responses have not always been satisfactory partially because of DC incompetence. In order to evaluate the feasibility of novel mature DCs for therapeutic adjuvants against CRC, we conducted clinical trials with carcinoembryonic antigen (CEA) peptide-loaded DC quickly generated with a combination of OK432 (Streptococcuspyogenes preparation), prostanoid, and interferon-α (OPA-DC). In the ten patients enrolled in this study, the OPA-DC vaccine was well tolerated and administered four times every 2 weeks except for two patients, who were switched to other treatments due to disease progression. Among the eight evaluable patients, one displayed stable disease (SD), while the remaining seven showed progressive disease (PD). In the SD patient, natural killer (NK) cell frequency and cytolytic activity were increased. In the same patient, the frequency of CEA-specific cytotoxic T cells (CTLs) increased stepwise with repetitive vaccinations; however, most of the CTLs exhibited central memory phenotype. In those with PD, NK cells proliferated well regardless of failure of response, whereas CTLs failed to do so. We concluded that the OPA-DC vaccine is well tolerated and has immune-stimulatory capacity in patients with CRC. Additional modulation is needed to attain significant clinical impact.

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Acknowledgments

We are grateful to the members of MTR, especially to the following Drs. Toshiki Yoshimine (Director), Yoshiki Sawa (Director), Akira Myoui (Vice Director), ChunMan Lee, Junji Kawada, Haruki Ide, and Masao Umegaki (Project Managers).

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Mitsuru Sakakibara, Tatsuya Kanto, Michiyo Hayakawa, Masanori Miyazaki, Naruyasu Kakita, Koyo Higashitani, Tokuhiro Matsubara, Naoki Hiramatsu & Tetsuo Takehara

  2. Department of Dendritic Cell Biology and Clinical Applications, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Tatsuya Kanto & Shoko Kuroda

  3. Osaka Police Hospital, Osaka, Japan

    Hideki Miyatake

  4. Kansai Rosai Hospital, Hyogo, Japan

    Ichiyo Itose & Norio Hayashi

  5. Department of General Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Akinori Kasahara

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  1. Mitsuru Sakakibara
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Correspondence to Tatsuya Kanto.

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Sakakibara, M., Kanto, T., Hayakawa, M. et al. Comprehensive immunological analyses of colorectal cancer patients in the phase I/II study of quickly matured dendritic cell vaccine pulsed with carcinoembryonic antigen peptide. Cancer Immunol Immunother 60, 1565–1575 (2011). https://doi.org/10.1007/s00262-011-1051-1

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