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Synergistic antitumour effects of chemo-immunotherapy with an oxazaphosphorine drug and IL-2-secreting cells in a mouse colon cancer model

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Abstract

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 nontumourigenic 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.

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Authors and Affiliations

  1. Department of Tumour Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 R Weigl Street, 53-114, Wrocław, Poland

    H Kusnierczyk, E Pajtasz-Piasecka & C Radzikowski

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  1. H Kusnierczyk
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  2. E Pajtasz-Piasecka
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  3. C Radzikowski
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Correspondence to H Kusnierczyk.

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Kusnierczyk, H., Pajtasz-Piasecka, E. & Radzikowski, C. Synergistic antitumour effects of chemo-immunotherapy with an oxazaphosphorine drug and IL-2-secreting cells in a mouse colon cancer model. Med Oncol 16, 267–278 (1999). https://doi.org/10.1007/BF02785873

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