title: Immune-maximizing (IMAX) therapy for cancer: Combination of dendritic cell vaccine and intensity-modulated radiation.
abstract: A dendritic cell (DC)-based vaccine was combined with intensity-modulated radiotherapy (IMRT) or other conformal radiotherapy (RT), assuming minimal immunosuppression by such RT modalities. In this study, the outcomes in the first 40 patients are presented. The patients had recurrent, metastatic or locally advanced tumors. Nine had previously undergone full-course RT. Peripheral blood mononuclear cells obtained by leukapheresis were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, OK-432 and prostaglandin E2 to generate DCs, which were pulsed with autologous tumor lysates or tumor-specific peptides, such as WT1. IMRT using tomotherapy, stereotactic irradiation or 3-dimensional conformal RT (3DCRT) was initially administered. The standard dose was 30 and 60 Gy in patients with and without previous RT, respectively. Every other week thereafter, up to a total of 7 times, DC vaccines were injected directly into the tumor (n=15) or administered intradermally when DCs were pulsed with tumor lysates or peptides. The tumor response was evaluated according to the response evaluation criteria in solid tumors (RECIST). RT and DC vaccines were well tolerated and there were no major complications. Three patients were not able to complete the planned DC therapy due to disease progression. For the 31 patients receiving full-dose RT, the response rate was 61% and for the 9 patients who had previously received RT, the response rate was 55%. In 9 patients, the tumor response outside the RT target volume was evaluable: 22% had a partial response (PR), 33% had stable disease (SD) and 44% had progressive disease (PD). In conclusion, a combination of IMRT (or 3DCRT) and DC vaccine is feasible and requires further investigation.
authors.affiliation: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Aichi 467-8601;
authors.forename: Yuta
authors.initials: Y
authors.lastname: Shibamoto
authors.affiliation: Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582;
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Aichi 467-8601; ; Seren Clinic Nagoya, Aichi 460-0008;
authors.forename: Masanori
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Radiology, Nagoya Daini Red Cross Hospital, Aichi 466-8650;
authors.forename: Shiho
authors.initials: S
authors.lastname: Ayakawa
authors.affiliation: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Aichi 467-8601;
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Iwata
authors.affiliation: Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Aichi 467-8601;
authors.forename: Chikao
authors.initials: C
authors.lastname: Sugie
authors.affiliation: Clinic Saint Louis, Kyoto 607-8011;
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mitsuishi
authors.affiliation: Seren Clinic Tokyo, Tokyo 108-0071, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Takahashi
keywords: dendritic-cell vaccine; immune-maximizing cancer therapy; intensity-modulated radiation therapy; stereotactic body radiotherapy