Cellular immunotherapy in late stage breast cancer patients with reactivated autologous Memory T-cells (MTC) derived from bone marrow (BM) (Phase-I trail)

We have previously shown an enrichment of tumor-specific MTC in BM in 66% of breast cancer patients by using ELISpot-analysis. Upon specific restimulation with dendritic cells (DC) in vitro BM T cells exert specific effector functions like IFN-gamma production and cytotoxicity. Furthermore we have shown in NOD/Scid-mice that reactivated MTC are able to kill tumor cells by induction of apoptosis (Nature Med, 2001). This effect required appropriate stimulation by tumor associated antigens (TAA), since MTC stimulated with irrelevant antigen did not exert anti-tumor effects in vivo. Furthermore we were able to show that endocrine and cytostatic cancer therapies only have a limited influence on the frequency of tumorspecific MTC in BM, so these cells still can be found in late stage breast cancer patients. We thus do a phase I trial with autologous reactivated MTC of BM in metastatic breast cancer patients. BM aspirate is tested by IFN-γ ELISPOT for MTCs that are reactive against TAA or lysate of breast cancer cell line (MCF-7). If reactive MTCs can be found these cells are reactivated by incubating them in vitro with autologous DC pulsed with TAA or MCF-7 lysate. Reactivated MTCs and pulsed DCs are then be injected intravenously into the same patient after 14 days of incubation time. Primary objectives are feasibility, determination of the effective dose and dose limiting toxicity; secondary objectives are quality of life, clinical response, and therapy efficiacy. We include only BC patients with measureable parameters or elevated tumormarkers, age 18 to 70 years. First experiences will be shown on this meeting.