Local immunotherapy of glioma patients with a combination of 2 bispecific antibody fragments and resting autologous lymphocytes: evidence for in situ t-cell activation and therapeutic efficacy

Int J Cancer. 2001 Jan 15;91(2):225-30. doi: 10.1002/1097-0215(200002)9999:9999<::aid-ijc1038>3.3.co;2-7.


After adoptive transfer of pre-activated lymphocytes into the operation cavity of glioma patients, tumor regression and improved survival have been reported in some patients. Results were most impressive when bispecific antibodies with tumor x CD3 specificity were also applied. In this study, we attempted to avoid time-consuming pre-activation procedures for adoptively transferred cells by using a combination of bispecific antibodies directed to the EGF receptor (EGFR) on tumor cells and to CD3 and CD28 on T cells. Eleven patients with high-grade malignant glioma received 3 injections of 2 bispecific antibody fragments (EGFR x CD3 and EGFR x CD28) together with freshly isolated autologous lymphocytes via an Ommaya reservoir. Intracavitary fluid aspirated during immunotherapy was examined for markers of T-cell activation. Increased levels of soluble IL-2 receptor and TNF-alpha were detected in the intracavitary fluid of all patients tested. Two of the 11 treated patients experienced a beneficial response to therapy as defined by a transient contrast enhancement in subsequent MRI scans and prolonged survival. Side effects were transient and consisted of fever, nausea, headache and aggravation of pre-existing neurologic deficits. These adverse effects were most likely due to the antibody construct containing anti-CD3 specificity. Two patients developed cerebral edema and required steroid treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bispecific / therapeutic use*
  • CD28 Antigens / immunology*
  • CD3 Complex / immunology*
  • ErbB Receptors / immunology*
  • Female
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • Immunotherapy, Adoptive*
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • Tumor Cells, Cultured


  • Antibodies, Bispecific
  • CD28 Antigens
  • CD3 Complex
  • ErbB Receptors