Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma.
A phase 1 study was conducted to assess the safety and immunologic response induced by direct injection of autologous immature dendritic cells (DCs) into tumor under radiotherapy in advanced hepatoma patients. Patients with advanced/metastatic stage hepatoma not suitable for surgery or transarterial embolization were enrolled. Groups of patients received two vaccinations. Each vaccination consisted of intratumoral injections of autologous immature DCs in four dose cohorts of 5 x 10(6), 1.5 x 10(7), 3 x 10(7), and 5 x 10(7) cells 2 days after a single fraction of conformal radiotherapy of 8 Gy. The second vaccination was performed 3 weeks later. Of the 14 patients entered, 12 completed two cycles of vaccination. The treatment was well tolerated at any of the dose levels. Six patients had mild transient fever (grade 1-2) with chill reactions, three patients developed grade 1 fatigue, and one patient developed mild myalgia and arthralgia after DC injections. There was no evidence of clinically manifested autoimmune disease. There were two partial responses and four minor responses. A decrease in the alpha-fetoprotein (AFP) level of more than 50% was found in three patients. Ten patients had completed immunologic response evaluation 2 weeks after the second cycle of vaccination. The AFP-specific immune response was evident in eight patients examined by cytokine release assay and in seven patients by ELISPOT assay. Six patients showed an increased NK cell cytotoxic activity after vaccination. These data suggest that the combination of intratumoral injection of DCs and conformal radiotherapy is safe and can induce tumor-specific and innate immunity.
Chi
Kwan-Hwa
KH
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan. M006565@ms.skh.org.tw
Liu
Shih-Jen
SJ
Li
Chung-Pin
CP
Kuo
Hsu-Ping
HP
Wang
Yu-Shan
YS
Chao
Yee
Y
Hsieh
Shih-Liang
SL
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases; D019496:Cancer Vaccines; D006528:Carcinoma, Hepatocellular / Q000532:radiotherapy* / Q000628:therapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000378:metabolism; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology; D008113:Liver Neoplasms / Q000532:radiotherapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020266:Radiotherapy, Conformal / Q000379:methods*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D000509:alpha-Fetoproteins / Q000378:metabolism
D019496:Cancer Vaccines; D016207:Cytokines; D000509:alpha-Fetoproteins; D007371:Interferon-gamma