This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schlick, E. Articles by Ruffmann, R. Search for Related Content PubMed PubMed Citation Articles by Schlick, E. Articles by Ruffmann, R.

Adjuvant Chemoimmunotherapy of Cancer: Influence of Tumor Burden and Role of Functional Immune Effector Cells in Mice

Laboratory of Molecular Immunoregulation [E. S., P. H.] and Biological Therapeutics Branch [R. R.], Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, NIH, Frederick Cancer Research Facility, Building 567, Room 220, Frederick, Maryland 21701

Starting from the observation that success of combined treatment of MBL-2 tumor-bearing mice with the alkylating agent cyclophosphamide (CY; 150 mg/kg) and the immunomodulator maleic anhydride divinyl ether copolymer (MVE-2; 25 mg/kg) was dependent upon a 1–3-day interval between treatment with CY and MVE-2, we have further analyzed in vitro and in vivo the relationship between tumor burden and the activity of immune effector cells in an adjuvant chemoimmunotherapy setting with CY and MVE-2. Treatment of MBL-2 tumor-bearing mice with CY (50–200 mg/kg) caused a dose- and time-dependent decrease in the i.p. tumor burden, which correlated with a significant increase in their median survival time. CY increased also the sensitivity of the residual MBL-2 tumor cells to Mø-mediated immunotherapy. The therapeutic efficacy of Mø-mediated immunotherapy with MVE-2, however, was restricted due to adverse effects of CY on the host's immune and hematopoietic functions. The time sequence with which these CY related positive effects on tumor burden and s(Tu)₁, as well as the adverse effects on macrophages and hematopoietic functions occurred, gives sufficient explanation for the narrow window in time for successful immunotherapy with MVE-2 after preceding chemotherapy with CY. We therefore propose to modify the conventional chemoimmunotherapy of MBL-2 tumor-bearing mice by combining it with an intermittent in vivo transfer of in vitro cultivated Mø (therapy sequence: CY Mø transfer MVE-2), which would result in an increased Mø:MBL-2 tumor cell ratio at the site of the tumor while reducing the adverse effects of CY on macrophage functions.

¹ To whom requests for reprints should be addressed. Present address: Dr. E. Schlick, Knoll AG, Unternehmen der BASF-Gruppe, Department of Oncology, 6700 Ludwigshafen, West Germany.

Received 12/20/85. Revised 3/25/86. Accepted 3/26/86.