Autologous fixed tumor vaccine: a formulation with cytokine-microparticles for protective immunity against recurrence of human hepatocellular carcinoma.
We developed a tumor vaccine consisting of fixed hepatocellular carcinoma (HCC) cells/tissue fragments, biodegradable microparticles encapsulating granulocyte-macrophage-colony stimulating factor and interleukin-2, and an adjuvant. The vaccine protected 33% of syngeneic mice from HCC cell challenge. The vaccine containing human autologous HCC fragments showed essentially no adverse effect in a phase I/IIa clinical trial and 8/12 patients developed a delayed-type hypersensitivity (DTH) response against the fragments. Although 2 of 4 DTH-response-negative patients had recurrence after curative resection, the DTH-response-positive patients had no recurrence. The time before the first recurrence in the vaccinated patients was significantly longer than that in 24 historical control patients operated in the same department (P < 0.05). This formulation is a promising candidate to prevent recurrence of human HCC.
Peng
Bao Gang
BG
RIKEN Cell Bank, RIKEN, The Institute of Physical and Chemical Research, Tsukuba Science City, Ibaraki 305-0074, Japan.
Liu
Shu Qin
SQ
Kuang
Ming
M
He
Qiang
Q
Totsuka
Saeri
S
Huang
Lan
L
Huang
Jiefu
J
Lu
Ming-De
MD
Liang
Li-Jiang
LJ
Leong
Kam W
KW
Ohno
Tadao
T
D000818:Animals; D019496:Cancer Vaccines / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000517:prevention & control / Q000628:therapy*; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000473:pathology* / Q000517:prevention & control / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D012008:Recurrence; D013997:Time Factors
D019496:Cancer Vaccines; D016207:Cytokines