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

التفاصيل البيبلوغرافية
العنوان: 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
المؤلفون: Jung, Gundram, Brandl, Martina, Eisner, Wilhelm, Fraunberger, Peter, Reifenberger, Guido, Schlegel, Uwe, Wiestler, Otmar D., Reulen, Hans-Jürgen, Wilmanns, Wolfgang
المصدر: International Journal of Cancer; 15 January 2001, Vol. 91 Issue: 2 p225-230, 6p
مستخلص: 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 × 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 × CD3 and EGFR × 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-α 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. © 2001 Wiley-Liss, Inc.
قاعدة البيانات: Supplemental Index
الوصف
تدمد:00207136
10970215
DOI:10.1002/1097-0215(200002)9999:9999<::AID-IJC1038>3.0.CO;2-G