Modified 2-Tumor (L1210, Colon 38) Assay to Screen for Solid Tumor Selective Agents

In 1983, the Cancer Research Department of The Upjohn Company and Dr. Tom Corbett (then at Michigan Cancer Foundation) initiated a collaborative effort to screen for agents selectively toxic to solid tumors. The need for this assay arose from the fact that the leukemic (L1210 and P388) cell lines used in vitro and in vivo as the primary screen for antitumor agents had produced substances that were primarily active against leukemias and lymphomas. This leukemia-oriented strategy had not generated agents significantly active against the common solid tumors such as lung, colon, pancreas, stomach, etc. For example, of more than 100 agents which were active against P388, only about 2% were active against Lewis lung carcinoma or colon 38 or human xenograft CX-1 (1,2). Corbett et al. (1,4) hypothesized that the vulnerability of P388 was different from that of the solid tumors. Therefore, they suggested that the specific vulnerability of tumor of a particular organ system would be detected only by models appropriate for that organ system (3). They proposed the 2-tumor assay to screen for compounds selectively toxic against solid tumors (4). In this assay, the lethality of the agent for L1210 cells was compared to lethality to cells from a drug-insensitive solid tumor (e.g. pancreatic adenocarcinoma 02, colon 38, etc.). The L1210 cells will identify agents toxic to rapidly growing cells, whereas the solid tumor cells will select new agents that are possibly solid tumor specific. This assay had two other advantages: (i) Primary expiants of tumor (instead of a cell line) were used in the assay. Cells from primary explants are much more likely to retain the characteristics of the original tumor than a cultured cell line, (ii) The ability of the cells to survive and form colonies was used as the end point. This is preferable to an indirect end point such as a colorimetric protein determination or a trypan-blue viability assay.