gms | German Medical Science

Tumorspecific Memory T-cells (MTC) can be found in the bone marrow (BM) in the majority of primary and metastatic breast cancer (BC) patients by using ELISpot-analysis. Upon specific restimulation with tumourantigen-pulsed dendritic cells (DC) those autologous T-cells exert specific effector functions like IFN-gamma or perforin production and specific cytotoxicity. Furthermore we have shown in NOD/Scid-mice that reactivated MTC are able to infiltrate autologous and heterologous tumor tissue, proliferate and kill tumor cells by induction of apoptosis, leading to a marked or complete tumor rejection within 21 days after transfer (Nature Med, 2001). Endocrine and cytostatic cancer therapies only have a limited influence on the frequency of tumorspecific MTC in BM of BC patients. In a phase-I trial 11 patients with metastatic BC (inclusion criteria) were treated with autologous reactivated MTC of BM. Primary objective were feasbility, and toxicity, secondary were clinical response, and immunomonitoring. After testing patient´s BM for presence of tumorspecific MTC those cells were reactivated by incubating them in vitro with autologous DC pulsed with MCF-7 lysate for 12 days. Reactivated T-cells and pulsed DCs were injected once intravenously. Follow Ups were done after 7, 14, 21, 28, and 120 days. Study design was feasible in every way. There were no side effects found during and after T-cell injection. There was a partial response in 3 of 5 measurable patients. In 5 Patients -who received a maximum of reactivated T-cells- we were still able to find those cells 7 days after vaccination. We conclude that cellular immunotherapy with autologous reactivated MTC is an innovative, feasible way of low-toxicity BC treatment. We thus prepare a phase-II trial in metastatic and primary BC patients.