For our experiments we selected two oncogenic, bcr-abl-transformed mouse cell lines, viz. B210 and 12B1. Both cell types are capable of inducing leukemia-like disease in syngeneic BALB/c mice after intravenous inoculation. 12B1 cells can moreover form solid tumors after subcutaneous injection. Since immunotherapy would expectedly be most effective in animals in which the tumor mass had been reduced by other therapeutic means, we attempted to develop a combined therapeutic system for suppressing tumor growth. In the present study, mice inoculated with the aggressive 12B1 cells were treated with imatinib mesylate (IM), mouse interferon alpha (IFNalpha) and cyclophosphamide (Cy) in combination with genetically modified tumor cells engineered to produce various cytokines. These cell vaccines had been derived from B210 cells. Therapy with IM or IFNalpha alone or cell immunotherapy alone resulted in partial suppression of tumor growth. Of the different therapeutic regimens tested, a combination of repeated doses of IM, IFNalpha and cell vaccines with one relatively high dose of Cy (200 mg/kg) was the most effective, resulting in tumor-free survival of a large portion of mice. The spleens, livers and bone marrows of the successfully treated animals were tested for the presence of bcr-abl-positive cells by means of RT-PCR technique. Results were negative, this suggesting that the animals had been cleared of residual disease.
- MeSH
- bcr-abl fúzní proteiny imunologie terapeutické užití MeSH
- benzamidy MeSH
- cyklofosfamid aplikace a dávkování MeSH
- experimentální nádory imunologie terapie MeSH
- faktor stimulující granulocyto-makrofágové kolonie biosyntéza MeSH
- imatinib mesylát MeSH
- imunoterapie metody MeSH
- interferon gama aplikace a dávkování MeSH
- interleukin-12 biosyntéza MeSH
- interleukin-2 biosyntéza MeSH
- kombinovaná terapie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- piperaziny aplikace a dávkování MeSH
- polymerázová řetězová reakce MeSH
- protinádorové látky aplikace a dávkování MeSH
- protinádorové vakcíny imunologie MeSH
- pyrimidiny aplikace a dávkování MeSH
- transformované buněčné linie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bcr-abl fúzní proteiny MeSH
- benzamidy MeSH
- cyklofosfamid MeSH
- faktor stimulující granulocyto-makrofágové kolonie MeSH
- imatinib mesylát MeSH
- interferon gama MeSH
- interleukin-12 MeSH
- interleukin-2 MeSH
- piperaziny MeSH
- protinádorové látky MeSH
- protinádorové vakcíny MeSH
- pyrimidiny MeSH
Microsporidia are eukaryotic, obligate, intracellular protists that are emerging pathogens in immunocompromised hosts, including AIDS patients and organ transplant recipients. The efficacy of gamma interferon (IFN-gamma) for the treatment of microsporidiosis caused by Encephalitozoon cuniculi was studied by means of adoptive transfer and IFN-gamma administration in SCID mice. While the adoptive transfer of CD4(+) T cells from immunocompetent mice prolonged survival of SCID mice infected perorally with E. cuniculi, survival was not improved by adoptive transfer of CD4(+) T lymphocytes from IFN-gamma-deficient mice. The protective effect of IFN-gamma was confirmed in cytokine therapy experiments in which SCID mice receiving IFN-gamma survived significantly longer than mice receiving mock injections. The administration of serum containing specific antibodies against E. cuniculi was found to prolong the survival of concurrently IFN-gamma-treated SCID mice. The data presented in this study suggest that IFN-gamma is potentially useful as a cytokine therapy for microsporidiosis, especially in CD4(+) T-cell-deficient patients.
- MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- Encephalitozoon cuniculi imunologie MeSH
- encephalitozoonóza imunologie mortalita parazitologie terapie MeSH
- imunoterapie MeSH
- interferon gama aplikace a dávkování genetika terapeutické užití MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- monoklonální protilátky imunologie terapeutické užití MeSH
- myši inbrední BALB C MeSH
- myši knockoutované MeSH
- myši SCID MeSH
- myši MeSH
- převzatá imunita MeSH
- specificita protilátek * MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interferon gama MeSH
- monoklonální protilátky MeSH
OBJECTIVE: Soluble recombinant human CD40 ligand trimer (rhuCD40Lt) has shown antitumor activity in preclinical and clinical studies. We evaluated the effect of rhuCD40Lt on epithelial ovarian carcinoma (EOC) cell lines. METHODS: Expression of the receptor, CD40, was determined by reverse transcriptase-polymerase chain reaction and flow cytometry, and antiproliferative effects of rhuCD40Lt, either alone or in combination with recombinant interferon-gamma (rIFN-gamma), were examined in 8 EOC lines. RESULTS: Expression of CD40 was elevated in 5 out of 8 EOC cell lines examined by flow cytometry, and the presence of CD40 transcripts was detected by RT-PCR in all 8 cell lines. CD40 expression was increased by rIFN-gamma, but treatment with rhuCD40Lt decreased CD40 expression in 4 of the 5 lines that had shown elevated CD40 expression. rhuCD40Lt had a growth-inhibitory effect on 2774 cells, which also exhibited the highest level of CD40 expression. Growth-inhibitory effect of rhuCD40Lt was additive with rIFN-gamma on 2774, NMP-1, a cisplatin-resistant subline of OVCAR3, and HEY cell lines. The number of apoptotic tumor cells was increased following treatment with rhuCD40Lt. CONCLUSIONS: CD40 is expressed on EOC cell lines, and expression was found at the transcript level in all of the EOC lines examined. rIFN-gamma enhances CD40 expression, though a decrease in CD40 expression was observed following treatment with rhuCD40Lt. Growth-inhibitory activity of rhuCD40Lt on EOC lines that express CD40 could be enhanced when rhuCD40Lt treatment was combined with rIFN-gamma. These results suggest that future studies of the combination of rhuCD40Lt and rIFN-gamma might warrant consideration.
- MeSH
- antigeny CD40 biosyntéza MeSH
- buňky - růstové procesy účinky léků MeSH
- interferon gama aplikace a dávkování MeSH
- lidé MeSH
- ligand CD40 aplikace a dávkování farmakologie MeSH
- nádorové buněčné linie MeSH
- nádory vaječníků farmakoterapie imunologie patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- protokoly protinádorové kombinované chemoterapie farmakologie MeSH
- průtoková cytometrie MeSH
- rekombinantní proteiny farmakologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny CD40 MeSH
- interferon gama MeSH
- ligand CD40 MeSH
- rekombinantní proteiny MeSH
Clinical impact of s.c. administration of IL-2 and/or IFN alpha was studied in 23 pediatric patients with Hodgkin lymphoma (IFN alpha group) and sarcoma, non-Hodgkin lymphoma, peripheral neuroepitelioma, neuroblastoma, and embryonic carcinoma (IL-2 + IFN alpha group) after autologous PBSC transplantation. Expression of CD3, CD4, CD8, CD25, CD38, CD56, CD71, CD122, and HLA-DR antigens, serum level of the soluble IL-2R alpha, and NK activity against K562 cell line were evaluated in 11 patients representative for both types of immunotherapy. T and, more markedly, NK cell proliferation, induction of activation markers on the surface of T and NK subsets, and elevation of sIL-2R alpha concentrations were seen in the IL-2 + IFN alpha subgroup. In the IFN alpha subgroup, the total number of lymphocytes and expression of activation markers remained unchanged, but the number of CD8+ T cells increased at the expense of CD4+ T and NK cells during the therapy. Cytotoxic activity against K562 cells was not influenced by the immunotherapy in either subgroup. No significant clinical benefit of the immunotherapy was seen in these patients compared to 27 control patients with relevant diagnoses who did not receive immunotherapy.
- MeSH
- autologní transplantace MeSH
- CD antigeny krev MeSH
- cytotoxicita imunologická MeSH
- dítě MeSH
- dospělí MeSH
- imunoterapie MeSH
- interferon gama aplikace a dávkování MeSH
- interleukin-2 aplikace a dávkování MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- mladiství MeSH
- nádory krev imunologie patofyziologie terapie MeSH
- protinádorové látky aplikace a dávkování MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- Názvy látek
- CD antigeny MeSH
- interferon gama MeSH
- interleukin-2 MeSH
- protinádorové látky MeSH
The intracellular growth of Legionella pneumophila in WiREF (Wistar rat embryonal fibroblast) cells was inhibited by porcine interferon-gamma. The effect was compared with that of different human interferons (alpha and gamma). The growth inhibition was dose-dependent and required the pretreatment of WiREF cells with interferon. The development of an antibacterial state of the cells was observed. When interferon was added together with bacteria or 1 d after the infection there was no inhibition. Also, there was no direct antibacterial effect of the interferon. In addition, cell pretreatment with a combination of interferon and antibiotics failed to show a synergistic effect.
- MeSH
- antibakteriální látky aplikace a dávkování farmakologie MeSH
- buněčné dělení účinky léků MeSH
- buněčné linie MeSH
- elektronová mikroskopie MeSH
- interferon gama aplikace a dávkování farmakologie MeSH
- interferon typ I aplikace a dávkování farmakologie MeSH
- krysa rodu Rattus MeSH
- Legionella pneumophila účinky léků růst a vývoj ultrastruktura MeSH
- lékové interakce MeSH
- lidé MeSH
- prasata MeSH
- rekombinantní proteiny MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- antibakteriální látky MeSH
- interferon gama MeSH
- interferon typ I MeSH
- rekombinantní proteiny MeSH