Adoptive immunotherapy of tumor- draining lymph node cells combined with low dose cyclophosphamide induces regression of established murine tumors.

ANDREA MAGLIOCO; DAMIÁN MACHUCA ; MUNDIÑANO JULIANA; GABRIELA CAMICIA; DRAN, GRACIELA

Viña del Mar

Congreso; 9th Latin American Congress of Inmunology; 2009

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+IFN+) 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.