Local injection of OK432 can augment the TH1-type T-cell response in tumor-draining lymph node cells and increase their immunotherapeutical potential.
The effect of local injections with streptococcal preparation OK432 on the therapeutical potential of tumor-draining lymph node (LN) cells was investigated in mice. Peritumoral injections with OK432 on days 2, 4, 6, 8 and 10 showed no effect on the in vivo growth of s.c. inoculated B16F10 melanoma. The B16F10-draining OK432-treated LN cells, however, showed a high level of anti-B16F10 cytolytic activity after an in vitro culture first with both anti-CD3 monoclonal antibody (MAb) and activated B cell blasts, and subsequently with interleukin (IL)-2 without in vitro restimulation. Such in vitro expanded LN cells showed a remarkable antitumor effect against pulmonary metastasis of B16F10 melanoma, even without the concurrent administration of IL-2. In addition, the therapeutical protocol was also found to be moderately effective against poorly immunogenic MCA fibrosarcoma, and the in vivo antitumor effect was specific to the tumor from which the LNs were harvested. Interestingly, 2 kinds of comparative analyses of the cytokines revealed that the B16F10-bearing state induced the draining LN cells to develop a Th2-type response. However, the OK432 treatment was able to effectively augment their Th1-type response. Collectively, our results suggest that peritumoral injections with OK432 significantly increased the therapeutical potential of the tumor-draining LN cells by augmenting their Th1-type response.
Okamoto
T
T
Department of Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Harada
M
M
Tamada
K
K
Yoshida
H
H
Ito
O
O
Kong
Y Y
YY
Takenoyama
M
M
Hirashima
C
C
Matsuzaki
G
G
Nomoto
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism; D010844:Picibanil / Q000008:administration & dosage / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000970:Antineoplastic Agents; D007376:Interleukin-2; D009363:Neoplasm Proteins; D015847:Interleukin-4; D010844:Picibanil; D007371:Interferon-gamma