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Pub. No.:    WO/2009/067375    International Application No.:    PCT/US2008/083331
Publication Date: 28.05.2009 International Filing Date: 13.11.2008
C12N 1/36 (2006.01)
Applicants: MEDICAL COLLEGE OF GEORGIA RESEARCH INSTITUTE, INC. [US/US]; 1120 15th Street, Ca-2125, Augusta, GA 30912 (US) (For All Designated States Except US).
IWASHIMA, Makio [JP/US]; (US) (For US Only).
SINGH, Nagendra [IN/US]; (US) (For US Only)
Inventors: IWASHIMA, Makio; (US).
SINGH, Nagendra; (US)
Agent: PABST, Patrea, L.; Pabst Patent Group LLP 400 Colony Square 1201 Peachtree Street, Suite 1200 Atlanta, GA 30361 (US)
Priority Data:
61/004,006 21.11.2007 US
Abstract: front page image
(EN)Methods for expanding regulatory T cells in vitro are provided. It has been discovered that regulatory T cells can be expanded in vitro by culturing a mixed population of lymphocytes on planar cell culture substrates, for example cell culture dishes, coated with binding partners for TCR complex and CD28. Remarkably, culturing mixed populations of lymphocytes on planar substrates coated with anti-CD3 and anti-CD28 antibodies induced apoptosis of effector T cells. It is believe that this is the first cell culture technique that expands regulatory T cells while inducing the apoptosis of effector cells in the mixed lymphocyte population using binding partners for cell surface proteins immobilized on planar substrate. Because effector T cells are typically present in mixed populations of lymphocytes, effector T cells compete with regulatory T cells and typically overtake the cell culture. The disclosed methods decrease the population of effector cells allowing regulatory T cells to expand by at least 100, typically by 400 fold. The resulting cultures of regulatory T cells have less than about 20%, 15%, or 10% of effector T cells.
(FR)L'invention concerne des procédés de multiplication de cellules T régulatrices in vitro. On a découvert que les cellules T régulatrices pouvaient être multipliées in vitro par culture d'une population mixte de lymphocytes sur des substrats de culture de cellules plans, par exemple des boîtes de culture de cellules, recouverts de partenaires de liaison du complexe TCR et de CD28. De manière remarquable, la culture de populations mixtes de lymphocytes sur des substrats plans recouverts d'anticorps anti-CD3 et anti-CD28 induit l'apoptose des cellules T effectrices. On pense qu'il s'agit là de la première technique de culture de cellules qui multiplie les cellules T régulatrices en induisant l'apoptose des cellules effectrices dans la population mixte de lymphocytes au moyen de partenaires de liaison pour les protéines de surface cellulaire immobilisés sur un substrat plan. Des cellules T effectrices étant généralement présentes dans les populations mixtes de lymphocytes, elles entrent en compétition avec les cellules T régulatrices et dominent généralement la culture cellulaire. Les procédés de l'invention réduisent la population de cellules effectrices en laissant les cellules T régulatrices se multiplier par au moins 100, généralement au moins 400. Les cultures de cellules T régulatrices obtenues contiennent généralement moins d'environ 20 %, 15 %, ou 10 % de cellules T effectrices.
Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
African Regional Intellectual Property Organization (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
Publication Language: English (EN)
Filing Language: English (EN)