Increased cancericidal activity of PTT.119; a new synthetic bis-(2-chloroethyl)amino-L-phenylalanine derivative with carrier amino acids. II. In vivo bioassay.

The cancericidal efficacy of a new synthetic tripeptide was demonstrated using both in vitro cultures and in vivo tumorigenic assays. The antitumor agent PTT.119 (p-F-Phe-m-bis-(2-chloroethyl)amino-Phe-Met ethoxy HCl) was highly effective against three virulent murine tumor models: the L1210 leukemia, MJY-alpha mammary tumor and B16 melanoma. Treatment of tumor cells for periods as short as 15 min to 4 h with concentrations of 1-50 micrograms PTT.119/ml irreversibly reduced tumor cell viability, as evidenced by vital dye exclusion and abrogation of tumor formation and prolongation of host survival. Examination of the sensitivity of mice to PTT.119 revealed that the in vitro antitumor activity of the synthetic tripeptide was exerted at concentrations easily attainable and well tolerated in vivo.