Intraperitoneal therapy of ovarian cancer with retargeted lymphocytes by bispecific monoclonal antibodies and interleukin-2

A. M.M. Eggermont, S. H. Goey, A. Logmans, J. B.M.Z. Trimbos, S. O. Warnaar, F. J. Cleton, C. H.J. Lamers, R. L.H. Bolhuis, G. Stoter

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Abstract

Background Ovarian cancer refractory to chemotherapy has a very poor prognosis and no standard treatment options. In a phase I-II study patients with recurrent disease restricted to the peritoneal cavity received intraperitoneal (i.p.) immunotherapy with interleukin-2 (IL-2) and autologous T-cells redirected by bispecific monoclonal antibodies (bs-MAb). Methods A bs-MAb with on the one hand specificity for ovarian cancer cells (the folate binding site MOv 18) and for the CD3 activation site on T-lymphocytes on the other, was produced in large quantities. Lymphocytes, obtained from the patient prior to debulking surgery, were cultured ex vivo and preincubated with the bs-Mab OC/TR (Ovarian Cancer-T cell Receptor) before i.p. administration. IL-2 was given i.p. every 12 hours at a dose of 600.000 IU. The first 4 days increasing numbers of T-cells were administered (106-109 cells), on days 7-11 and 28-32, 109 redirected T-cells were administered each day. Evaluation for tumor response was done by laparotomy 6 weeks after i.p. treatment. Results 11 patients entered the protocol; 10 were evaluable for toxicity; 3 had extracavitary progression without signs of i.p. progression, but were not explored. Therefore in 7 patients i.p. tumor response was evaluated by laparotomy: i.p. CRs were observed in 2 patients, in 1 however there was concurrent PD in retroperitoneal lymph nodes; furthermore 2PRs, 1 SD and 2 PDs were observed. Toxicity was mild, limited to grade 2 fever, abdominal discomfort, tenderness, bloating, and grade 1-2 nausea. Conclusions Immunotherapy with T-cells redirected by bs-Mabs in ovarian cancer has therapeutic potential and should be explored further.

Original languageEnglish
Pages (from-to)90-92
Number of pages3
JournalActa Chirurgica Austriaca
Volume27
Issue number2
DOIs
Publication statusPublished - Mar 1995
Externally publishedYes

Keywords

  • bispecific antibodies
  • immunotherapy
  • intraperitoneal
  • Ovarian cancer
  • T-cells

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