Synergistic antitumour effects of chemo-immunotherapy with an oxazaphosphorine drug and IL-2-secreting cells in a mouse colon cancer model
| Autor: | C Radzikowski, Elżbieta Pajtasz-Piasecka, Halina Kusnierczyk |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Interleukin 2
Cancer Research Cyclophosphamide medicine.medical_treatment Immunology Intraperitoneal injection Adenocarcinoma Pharmacology Immunotherapy Adoptive Mice chemistry.chemical_compound Chemoimmunotherapy Tumor Cells Cultured medicine Animals Immunology and Allergy Ifosfamide Antineoplastic Agents Alkylating Chemotherapy business.industry Drug Synergism Immunotherapy Combined Modality Therapy Nitrogen mustard Mice Inbred C57BL Oncology chemistry Mice Inbred DBA Colonic Neoplasms Interleukin-2 Female business Neoplasm Transplantation Plasmacytoma medicine.drug |
| Zdroj: | Medical Oncology. 16:267-278 |
| ISSN: | 1432-0851 0736-0118 |
| DOI: | 10.1007/bf02785873 |
| Popis: | The therapeutic efficacies of two chemical agents-cyclophosphamide (CY) and compound CBM-11-were compared in a chemo-immunotherapy protocol combining a single injection of a cytotoxic agent with a series of weekly peritumoural (p.t.) administrations of non-tumourigenic plasmocytoma cells engineered to produce interleukin-2 (IL-2). Compound CBM-11, an optically active S(-) isomeric form of a bromine-substituted analogue of ifosfamide, is currently used in Phase I clinical trials in Poland. The treatment was applied to mice bearing well-established subcutaneous (s.c.) MC-38 colon tumours. Single intraperitoneal injection of 200 mg/kg of CY or of an equitoxic dose of 140 mg/kg of CBM-11 alone resulted in a tumour growth delay (TGD) of 10-13 and 17-21 d, respectively. This effect was accompanied by an increase in life-span (ILS) of at most 42 and 62% over control. Complete responses (CR) were not observed. Combination of CY or CBM-11 with 6-7 p.t. injections of IL-2-secreting cells resulted in potentiation of the therapeutic effects: TGD and ILS values were considerably increased and long-lasting CRs were observed. The overall incidence of CR after combined treatment was ca 16% and 42% for CY and CBM-11, respectively (P=0.049). A specific anti-MC-38 immunity was induced by the treatment, as verified by rechallenge of cured mice with MC-38 tumour cells 3-4 months post therapy cessation. Our results indicate that tumour destruction by chemotherapy (even if not complete) and prolonged local delivery of IL-2 secreted by allogeneic cells of an easy to culture line are sufficient to secure long-lasting specific antitumour immunity in cured mice. |
| Databáze: | OpenAIRE |
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