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Publication Year: 2000

1795

Adoptive Immunotherapy in Ovarian Cancer with Monocyte Derived Activated Killer Cells Mixed with Anti HER2/neu + Anti Fc Gamma RI Bispecific Antibody. A de Gramont, D Gangji, C Louvet, Ml Garcia, D Tardy, Jl Romet-Lemonne, Hosp St Antoine, Paris, France; Erasme Hosp, Brussels, Belgium; IDM, Paris, France.

Aim: To assess the safety and the efficacy of intraperitoneal (i.p.) injections of monocyte derived activated killer cells (MAK) mixed with anti HER2/neu + anti Fc gamma RI bispecific monoclonal antibody on the residual disease (RD) of ovarian cancer after surgery and chemotherapy. Patients and method: Following 2nd look examination after surgery and chemotherapy, patients with microscopic (positive biopsy) or macroscopic (< 1 cm) RD were included. They received 6 i.p. of autologous MAK cells mixed with a humanised bispecific antibody anti HER2/neu + anti Fc gamma RI (MDX 210 - Medarex). Mononuclear cells obtained by apheresis were cultured during 6 days with GM-CSF using the MAK cell Processor (IDM). They were then activated by g-interferon for 16 hours and elutriated. At the end of the procedure, about 1 milliard MAK cells with > 90% purity and viability were collected and injected i.p. using a subcutaneous chamber and an intraperitoneal catheter. Efficacy was evaluated at the time of a 3rd look performed 3 months after initiation of cell therapy. Results: 14 eligible patients were included between December 1997 and June 1999. 8 patients demonstrated HER2/neu overexpression at the surface of ovarian tumor cells. At the time of the 3rd look, progressive disease was observed in 5 patients, no change in 3 and a complete clinical response was seen in 6 patients (including multiple negative biopsies in 5). No serious adverse events related to therapy nor grade 3 / 4 (NCI-CTC) side effect occurred during the apheresis and the treatment. Conclusion: Treatment with monocyte derived activated killer cells mixed with anti HER2/neu + anti Fc gamma RI monoclonal bispecific antibody appeared to be feasible and safe. Further controlled studies are required to confirm efficacy.

 

 

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