Non-cell Corynebacterium parvum generated by nanotechnology: A promising immunomodulator with less side effects

Abstract

Corynebacterium parvum (CP), a kind of immunomodulator, has been well documented in immunotherapy to tumor. However, severe side effects, such as intrahepatic granulomas and scleromes 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 sclerome 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-α(TNF-α) but high level of interferon-γ (IFN-γ), an inhibitor to fibrosis. Our study has led to the view that NCPP will evolve into a new valuable immunomodulator for clinical application.

Systemic toxicity of non-cell corynebacterium parvum (CP) in monkeys

“…* P < 0.05 vs NS group, * * P < 0.01 vs NS group. Study indicated that increasing of spleen coefficient had a remarkable positive correlation with anti-tumor effects of CP and NCPP (Gao et al, 2007;Chare et al, 1977). In the present study, no significant difference was found in spleen coefficient, although spleen coefficients of NCPP and CP groups were higher than that of NS group (data not shown).…”

“…In vivo experiment indicates that NCPP cause no scleromes at the site of injection when administrated by intramuscular injection. Liver injury caused by NCPP is slighter than that caused by CP (Gao et al, 2007). To our knowledge, no data has been available on the systematic evaluation of its immunogenicity and systemic toxicity.…”

“…Results showed that NCPP posses multiple pharmacological actions, including anti-tumor activity, antiviral activity and anti-tuberculosis activity in vitro and in vivo (Gao et al, 2003a(Gao et al, , 2003b(Gao et al, and 2004. It maintains strong anti-tumor effects of CP and can enhance the phagocytic capacity of macrophage (Gao et al, 2007). In vivo experiment indicates that NCPP cause no scleromes at the site of injection when administrated by intramuscular injection.…”

NCPP treatment alleviates ConA-induced hepatitis via reducing CD4+T activation and NO production

“…NCPP was prepared as mentioned earlier (12) . The level of endotoxin that contaminated NCPP was provided with a Tachypleus Amebocyte Lysate ES-Test assay and found to be not more than 0.25 EU/mL.…”

“…Our previous study proved that NCPP had good immunoregulatory function and low side effects. (12) Since NCPP is a new immune regulator, we hypothesize that it may play crucial roles in Con A-induced hepatitis. At present, we demonstrated that pretreatment with low dose of NCPP could effectively suppress ConA-induced murine severe hepatitis, and this inhibitory effect was partly dependent on down-regulating the activation of hepatic CD4+T cells and inhibiting of macrophages, especially hepatic Kuffer cells to secrete NO.…”