Characterization of the exogenous interleukin-2 requirements for the generation of enhanced antitumor cytotoxicity by thymocytes from low-dose melphalan-treated MOPC-315 tumor bearers

• Published in: Cancer Immunology Immunotherapy Vol. 36; no. 1; pp. 37 - 44
• Main Authors: RUBIN, M, MOKYR, M. B
• Format: Journal Article
• Language: English
• Published: Berlin Springer 1993; Springer-Verlag
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Drug Screening Assays, Antitumor; Female; General aspects; Interleukin-2 - therapeutic use; Medical sciences; Melphalan - therapeutic use; Mice; Mice, Inbred BALB C; Original; Pharmacology. Drug treatments; Plasmacytoma - drug therapy; Recombinant Proteins - therapeutic use; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Antineoplastic agent; Thymocyte; Low dose; Rodentia; Cytokine; Cytotoxicity; Malignant tumor; In vitro; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Interleukin 2; Mouse; Animal; T-Lymphocyte; Plasmacytoma; Tumor cell
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/BF01789129

We have shown previously that thymocytes from MOPC-315-tumor-bearing mice treated with low-dose melphalan (L-phenylalanine mustard) (L-PAM TuB mice) are superior to thymocytes from untreated MOPC-315-tumor-bearing mice or thymocytes from untreated normal mice or normal mice treated with low-dose melphalan in their ability to generate an antitumor cytotoxic response following 5-day in vitro stimulation with MOPC-315 tumor cells in the presence of a low concentration of recombinant interleukin-2 (rIL-2) [Mokyr MB, Bartik MM, Ahn M-C (1989) Cancer Res 49; 870]. Here we characterize the rIL-2 requirements for the generation of enhanced antitumor cytotoxicity by L-PAM TuB thymocytes relative to normal thymocytes upon in vitro stimulation with MOPC-315 tumor cells. Specifically, we show that delaying the addition of a low concentration of rIL-2 to 5-day in vitro stimulation cultures of thymocytes resulted in a progressive decline in the generation of antitumor cytotoxicity by both normal and L-PAM TuB thymocytes. However, even when rIL-2 was added on day 2 after culture initiation, thymocytes from L-PAM TuB mice generated a more potent antitumor cytotoxicity than did thymocytes from normal mice. In addition, when rIL-2 was added at the time of culture initiation, replacement of the conditioned medium with fresh medium lacking rIL-2 on day 3 of the 5-day in vitro stimulation culture period eliminated the ability of normal thymocytes, and reduced (but did not eliminate) the ability of L-PAM TuB thymocytes, to generate a significant level of antitumor cytotoxicity. A low concentration of fresh rIL-2 was sufficient to restore completely the generation of antitumor cytotoxicity by normal or L-PAM TuB thymocytes when added to the stimulation cultures immediately after the removal of the rIL-2-containing conditioned medium. The same low concentration of rIL-2 was also sufficient for restoring the generation of antitumor cytotoxicity by cultures of L-PAM TuB thymocytes, but not normal thymocytes, from which the rIL-2-containing medium was removed 1 day earlier. At the same time, conditioned medium from stimulation cultures of L-PAM TuB thymocytes was not superior to conditioned medium from stimulation cultures of normal thymocytes in supporting the generation of antitumor cytotoxicity by either normal or L-PAM TuB thymocytes.