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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
Author(s) -
Jung Gundram,
Brandl Martina,
Eisner Wilhelm,
Fraunberger Peter,
Reifenberger Guido,
Schlegel Uwe,
Wiestler Otmar D.,
Reulen HansJürgen,
Wilmanns Wolfgang
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1038>3.0.co;2-g
Subject(s) - medicine , glioma , immunotherapy , cd3 , cd28 , antibody , adoptive cell transfer , t cell , immunology , pathology , cancer research , immune system , cd8
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.