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Cancers 2011, 3(2), 2223-2242; doi:10.3390/cancers3022223

Therapeutic Response in Patients with Advanced Malignancies Treated with Combined Dendritic Cell–Activated T Cell Based Immunotherapy and Intensity–Modulated Radiotherapy

1
Hasumi International Research Foundation, Tokyo Research Center, 1-44-6 Asagaya-kita, Suginami- ku, Tokyo 166-0001, Japan
2
Department of Pathology, University of Maryland School of Medicine, MSTF Room 700, 10 South Pine Street, Baltimore, Maryland 21040, USA
*
Author to whom correspondence should be addressed.
Received: 7 March 2011 / Revised: 14 April 2011 / Accepted: 19 April 2011 / Published: 28 April 2011
(This article belongs to the Special Issue Cancer Vaccines and Immunotherapy)
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Abstract

Successful cancer immunotherapy is confounded by the magnitude of the tumor burden and the presence of immunoregulatory elements that suppress an immune response. To approach these issues, 26 patients with advanced treatment refractory cancer were enrolled in a safety/feasibility study wherein a conventional treatment modality, intensity modulated radiotherapy (IMRT), was combined with dendritic cell-based immunotherapy. We hypothesized that radiation would lower the tumor burdens, decrease the number/function of regulatory cells in the tumor environment, and release products of tumor cells that could be acquired by intratumoral injected immature dendritic cells (iDC). Metastatic lesions identified by CT (computed tomography) were injected with autologous iDC combined with a cytokine-based adjuvant and KLH (keyhole limpet hemocyanin), followed 24 h later by IV-infused T-cells expanded with anti-CD3 and IL-2 (AT). After three to five days, each of the injected lesions was treated with fractionated doses of IMRT followed by another injection of intratumoral iDC and IV-infused AT. No toxicity was observed with cell infusion while radiation-related toxicity was observed in seven patients. Five patients had progressive disease, eight demonstrated complete resolution at treated sites but developed recurrent disease at other sites, and 13 showed complete response at various follow-up times with an overall estimated Kaplan-Meier disease-free survival of 345 days. Most patients developed KLH antibodies supporting our hypothesis that the co-injected iDC are functional with the capacity to acquire antigens from their environment and generate an adaptive immune response. These results demonstrate the safety and effectiveness of this multimodality strategy combining immunotherapy and IMRT in patients with advanced malignancies. View Full-Text
Keywords: dendritic cells; activated T-cells; combination immunotherapy; intratumoral injection; cancer vaccine dendritic cells; activated T-cells; combination immunotherapy; intratumoral injection; cancer vaccine
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Hasumi, K.; Aoki, Y.; Watanabe, R.; Hankey, K.G.; Mann, D.L. Therapeutic Response in Patients with Advanced Malignancies Treated with Combined Dendritic Cell–Activated T Cell Based Immunotherapy and Intensity–Modulated Radiotherapy. Cancers 2011, 3, 2223-2242.

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