Autogenic IL-10 modified dendritic cells in immune therapy of multiple sclerosis: the first clinical experience
- Authors: Odinak M.M.1, Chirsky V.S.1, Bisaga G.N.1, Baldueva I.A.2, Moiseenko V.M.2, Nekhaeva Т.L.2, Kalinina N.M.3, Davydova N.I.3, Bychkova N.V.3, Ciumas C.4
-
Affiliations:
- S.M. Kirov Military Medical academy
- N.N. Petrov Research Institute of Oncology
- Nikiforov Russian Center of Emergency and Radiation Medicine
- Epilepsy Research Center
- Issue: Vol 3, No 4 (2008)
- Pages: 60-65
- Section: Clinical experience
- URL: https://genescells.ru/2313-1829/article/view/217712
- ID: 217712
Cite item
Open Access
Access granted
Abstract
The search of effective therapy for multiple sclerosis CMS) that is the most common demyelinating disorder of the central nervous system affecting young people leading to their disability is still actual. The cumulative data as well as clinical experience of dendritic cells CDCs) usage in oncology facilitated a pilot investigation - a clinical study of the I phase of autogenic IL-10 modified DCs usage in immune therapy of MS.
A course of experimental immune therapy was given to a 46 year old man with secondary progressive MS who had failed to respond to combined treatment including specific standard immune therapy with copaxone and nonspecific antioxidant neuroprotective and corticosteroid therapy. A single dose of autogenic IL-10 modified dendritic cells in the amount of 3x106was injected subcutaneously into the patient’s back and was thrice-repeated in 4 months at successive intervals of a month. The first results showed that in the absence of any local side effects the immune system response to the administration of these cells was rather complex with the participation of T- and B- cells. The decline of the antibody titres to myelin basic protein was most significant that can be considered as an evidence of formation of immune tolerance to this protein along with relative and absolute increase of a peripheral blood regulatory T-lymphocytes CCD4+CD25+) number. However, relevant alterations of the patient’s clinical and neurologic status did not occur after the course of autogenic IL-10 modified DCs had been given. The data received allow to consider further investigations of the proposed method of specific immune therapy appropriate in order to assess its tolerance*, safety and mechanisms of DCs effects on patients with MS.
Full Text
About the authors
M. M. Odinak
S.M. Kirov Military Medical academy
Author for correspondence.
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
V. S. Chirsky
S.M. Kirov Military Medical academy
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
G. N. Bisaga
S.M. Kirov Military Medical academy
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
I. A. Baldueva
N.N. Petrov Research Institute of Oncology
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
V. M. Moiseenko
N.N. Petrov Research Institute of Oncology
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
Т. L. Nekhaeva
N.N. Petrov Research Institute of Oncology
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
N. M. Kalinina
Nikiforov Russian Center of Emergency and Radiation Medicine
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
N. I. Davydova
Nikiforov Russian Center of Emergency and Radiation Medicine
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
N. V. Bychkova
Nikiforov Russian Center of Emergency and Radiation Medicine
Email: bozo.ilya@gmail.com
Russian Federation, Saint Petersburg
C. Ciumas
Epilepsy Research Center
Email: bozo.ilya@gmail.com
France, Lyon
References
- Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol. Sci. 2001; 22 (2): 117-39.
- Hernandes M.A. Epidemiology of multiple sclerosis. Controversies and realities. Rev. Neurol. 2000; 30 (10): 959—64.
- Trapp B.D., Peterson J., Ransohoff R.M. et al. Axonal transection in the lesions of multiple sclerosis. N. Ingl. J. Med. 1998; 338 (5): 278—85.
- Fox R.J., Cohen J.A. Multiple sclerosis: the importance of early recognition and treatment. Cleve. Clin. J. Med. 2001; 68: 157—71.
- Xiao B.G., Huang Y.M., Link H. Tolerogenic Dendritic Cells: The Ins and Outs of Outcome J. Immunother. 2006; 29: 465—71.
- Stbve 0., Cravens P.D., EagarT.N. DNA-based vaccines: the future of multiple sclerosis therapy? Expert Rev. Neurother. 2008; 8: 351—60.
- Duan R.S., Link H., Xiao B.G. Long-term effects of IFN-γ, IL-10 and TGF-β-modulated dendritic cells on immune response in Lewis rats. J. Clin. Immunol. 2005; 25: 50—5.
- Моисеенко B.M., Балдуева И.А., Орлова P.B., Семенова А.И. Способ иммунотерапии костно-мозговыми дендритными клетками больных солидными опухолями. Авторское свидетельство на изобретение № 2203683.
- Балдуева И.А. Противоопухолевые вакцины. Практическая онкология 2003; 3: 157—66.
- Моисеенко В.М., Балдуева И.А., Данилова А.Б. и др. Шестилетний опыт вакцинотерапии злокачественных опухолей. Мед. иммунология 2004; 6 (3-5): 458.
- Steinbrink К., Wolfl М., Jonuleit Н. et al. Induction of tolerance by IL-1 О-treated dendritic cells. J. Immunol. 1997; 159: 4772—80.
- Steinman R.M., HawigerD., Nussenzweig M.C. Tolerogenic dendritic cells. Annu. Rev. Immunol. 2003; 21: 685-711.
- Lutz M.B., Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 2002; 23: 445-9.
- Taams L.S., Akbar A.N. Peripheral generation and function of CD4+CD25+ regulatory T cells. Curr. Top Microbiol. Immunol. 2005; 293: 115-31.
- Serody J.S., Collins E.J., Tisch R.M. et al. T cell activity after dendritic cell vaccination is dependent on both the type of antigen and the mode of delivery. J. Immunol. 2000; 164: 4961—7.
- Corinti S., Albanesi C., la Sala A. et al. Regulatory activity of autocrine IL-10 on dendritic cell functions. J. Immunol. 2001; 166: 4312-4318.
- Rutella S., Bonanno G., Pierelli L. et al. Granulocyte colonystimulating factor promotes the generation of regulatory DC through induction of IL-10 and IFN-alpha. Eur. J. Immunol. 2004; 34: 1291—302.
Supplementary files
