Local antitumour treatment in carcinoma patients with bispecific-monoclonal-antibody-redirected T cells

Autor: B. J. Kroesen, A. ter Haar, H. Spakman, P. Willemse, D. Th. Sleijfer, E. G. E. de Vries, N. H. Mulder, H. H. Berendsen, P. C. Limburg, T. H. The, L. de Leij
Rok vydání: 1993
Předmět:
Male
Cancer Research
medicine.medical_treatment
Lymphocyte
T-Lymphocytes
Fluorescent Antibody Technique
Pilot Projects
ADHESION
Lymphocyte Activation
THERAPY
Immunotherapy
Adoptive
Carcinoembryonic antigen
Cell Movement
HYBRID HYBRIDOMAS
Immunology and Allergy
Ascitic Fluid
TUMOR-INFILTRATING LYMPHOCYTES
T CELL TARGETING
Bispecific monoclonal antibody
biology
Antibodies
Monoclonal
Middle Aged
Intercellular Adhesion Molecule-1
CANCER
TARGET
medicine.anatomical_structure
C-Reactive Protein
Oncology
Tumor necrosis factor alpha
Female
CARCINOMA
medicine.drug_class
BISPECIFIC MONOCLONAL ANTIBODIES
ANTIGEN
Immunology
Monoclonal antibody
INFLAMMATION
Antigen
Antigens
CD
medicine
Animals
Humans
IMMUNOTHERAPY
Aged
LYSIS
business.industry
Tumor-infiltrating lymphocytes
Interleukin-6
Tumor Necrosis Factor-alpha
RECOGNITION
PATHWAYS
Immunotherapy
Carcinoembryonic Antigen
Pleural Effusion
Malignant
Abdominal Neoplasms
T CELL ACTIVATION
Cancer research
biology.protein
business
Cell Adhesion Molecules
Granulocytes
Zdroj: Cancer Immunology Immunotherapy, 37(6), 400-407. SPRINGER
ISSN: 0340-7004
Popis: In a pilot clinical study carcinoma patients with malignant ascites or pleural exudates have been treated locally with autologous lymphocytes activated ex vivo and redirected towards tumour cells with bispecific monoclonal antibodies. BIS-1, the bispecific monoclonal antibody used in this study, combines specificity against a tumour-associated antigen, AMOC-31, present on carcinomas, with a specificity against the CD3 complex on T lymphocytes. Patients selected for treatment had malignant pleural or peritoneal effusions. Treatment consisted of isolating autologous peripheral blood lymphocytes, ex vivo activation, incubation with bispecific monoclonal antibodies and injection at the effusion site of these BIS-1-redirected lymphocytes. To evaluate the effects of the bispecific monoclonal antibody, five patients received treatments with activated lymphocytes without bispecific antibodies. Effusion samples taken before and at various times after treatment were analysed by immunocytology and for the presence of the soluble factors carcinoembryonic antigen (CEA), interleukin-6 (IL-6), tumour necrosis factor (TNF), C-reactive protein and soluble CD8. In this way both immune activation and anti-tumour activity could be monitored. Conjugate formation between tumour cells and activated lymphocytes was seen as soon as 4 h after injection of BIS-1-redirected activated lymphocytes, followed by a disappearance or reduction of tumour cells after 24-48 h. In parallel with this, the soluble tumour marker CEA decreased in the effusion fluid following injection with the BIS-1-redirected lymphocytes. Furthermore, a steep increase in local granulocyte numbers was observed in the effusion fluid, which reached a maximum 24-48 h after the start of the treatment. Also levels of IL-6 and TNF were greatly elevated. The data suggest that the treatment induces both antitumour activity and a strong local inflammatory reaction. This is accompanied by no or only minor local and systemic toxicity, i.e. mild fever, which disappeared as the local inflammatory reaction diminished 48-72 h after treatment.
Databáze: OpenAIRE
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