Non-cell Corynebacterium parvum generated by nanotechnology: a promising immunomodulator with less side effects.
Corynebacterium parvum (CP), a kind of immunomodulator, has been well documented in immunotherapy to tumor. However, severe side effects, such as intrahepatic granulomas and scleromas in injected areas, restrict its clinical application. To minimize side effects of CP, a non-cell Corynebacterium parvum product (NCPP) was prepared by disposing CP with Nanotechnology. In present study, we compared effect of NCPP with that of CP and found: (1) NCPP with non-formaldehyde residue was easy to be absorbed without swelling and scleroma in local injected areas; (2) NCPP caused no obvious liver injury in murine and macaques; (3) NCPP maintained powerful anti-tumor activity, increased splenic index, elevated macrophage number, phagocytosis and production of hydrogen peroxide (H(2)O(2)), and nitric oxide (NO); (4) Importantly, unparallel CP, NCPP could stimulate macrophages to produce low level of tumor necrosis factor-alpha(TNF-alpha) but high level of interferon-gamma (IFN-gamma), an inhibitor to fibrosis. Our study has led to the view that NCPP will evolve into a new valuable immunomodulator for clinical application.
Gao
Shangxian
S
Department of Medium, National Institute for the Control of Pharmaceutical and Biological Products, Beijing, PR China.
Liu
Chenghu
C
Qu
Shoufang
S
Song
Jing
J
Li
Jianfeng
J
Zhang
Pin
P
Wang
Qun
Q
Guo
Chun
C
Gao
Fei
F
Zhang
Lining
L
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D006861:Hydrogen Peroxide / Q000378:metabolism; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008251:Macaca; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D036103:Nanotechnology; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011425:Propionibacterium acnes / Q000276:immunology*; D011817:Rabbits; D047368:Tumor Burden / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000970:Antineoplastic Agents; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase