INVESTIGADORES
MAGLIOCO andrea Florencia
congresos y reuniones científicas
Título:
Adoptive immunotherapy of tumor- draining lymph node cells combined with low dose cyclophosphamide induces regression of established murine tumors
Autor/es:
ANDREA MAGLIOCO; MACHUCA D; MUNDIÑANO J; CAMICIA G; DRAN G
Reunión:
Congreso; 9th Latin American Congress of Inmunology; 2009
Resumen:
Tumors often impair immune
recognition and rejection by inducing immunological tolerance, which favors
tumor progression and constitutes a main obstacle against immunotherapies.
Determining the mechanisms governing tolerance is therefore a needed step for
successful immunological trials. The MCC experimental murine tumor progresses
from a strongly immunogenic to a tolerogenic state. We first aimed to study the
effects of MCC development on the host immune cells within the tumor draining
and tumor distal lymph nodes. We found that activated lymphocytes (CD8+IFNg+) and suppressor cells
(CD4+CD25+Foxp3+ and B220+IL10+)
coexist within the lymph node draining established tumors. We therefore
designed a protocol combining a low dose of cyclophosphamide (50mg/Kg), which
was not tumoricidal but depleted B and regulatory T cells, followed by tumor
draining lymph node excision and adoptive transference of the lymph node cells,
previously cultured and stimulated to expand tumor- primed cytotoxic cells.
Transferred cells consisted mainly of CD4 and CD8 T lymphocytes and showed
in vitro and in vivo specific cytotoxicity. The combined treatment induced
complete tumor rejection in 65% of the treated mice, tumor volumes ranging from
150 to 300 mm3. These results raise the possibility of using autologous excised
cells to treat the tumor with a low
toxicity.