Induction of a T- and B-cell response against a unique amino acid sequence of the mouse IgG2A hinge region in a MAb-treated patient.
A patient with malignant glioblastoma was treated with intratumoral infusions of the murine MAb425 (IgG2A) directed against the epidermal growth factor receptor. At the 10th infusion, the patient developed somnolence, fever and headache. The symptoms increased during the subsequent 48 hr but then gradually disappeared within a week. The cerebrospinal fluid (CSF) contained increased concentrations of interleukin-2. The main CSF cell subset was CD4 T-cells. A marked blood lymphocyte proliferative response against mouse IgG2A was noted. The reactive T-cell epitope(s) could be localized to a 14 amino acid (RGPTIKPCPPCKCP) long peptide of the hinge region. A B-cell response (IgG antibodies) against this peptide was also induced.
Wersäll
P
P
Department of Oncology (Radiumhemmet), Karolinska Hospital, Stockholm, Sweden.
Fagerberg
J
J
Ohlsson
I
I
Rudén
U
U
Boethius
J
J
Mellstedt
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000166:cytology; D004247:DNA / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000276:immunology; D005434:Flow Cytometry; D005909:Glioblastoma / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D004247:DNA; D066246:ErbB Receptors