The influence of 2- chlorodeoxyadenosine in combination with tumour necrosis factor-α or its mutein on murine leukaemias L1210 and P388

We investigated the influence of 2-chlorodeoxyadenosine (2-CdA) in combination with tumour necrosis factor-α (TNFα) or its mutein VI, which differs from the native molecule by N-terminal amino acid composition, on the survival time of mice inoculated with leukaemia L1210 or P388. Groups of mice with leukaemia L1210 and P388 receiving 2-CdA combined with TNFα had shorter survival times than animals treated with these agents separately. In contrast, the administration of 2-CdA in conjunction with mutein VI, prolonged the survival of mice inoculated with these leukaemias as compared with animals receiving these agents separately. The results of the present study emphasize the importance of the biological activity of the TNFα molecule N-terminus

A comparison of the Antileukaemic Effects of Recombinant Human Tumour Necrosis Factor-α and its Muteins on Leukaemia L1210 and Leukaemia P388 in Mice

We investigated the influence of recombinant human tumour necrosis factor alpha (TNF-α) and its derivatives termed muteins III, V, VI—in which the first 3 to 7 amino acids of native TNF-α have been replaced—on the survival time of mice inoculated with leukaemia L1210 or leukaemia P338. TNF-α prolonged the survival of mice with leukaemia L1210 but did not have any therapeutic activity in leukaemia P388-bearing mice. Muteins-treated mice with leukaemia P388 lived longer than animals receiving TNF-α, while those inoculated with leukaemia L1210 did not show any significant prolongation of life compared with the TNF-α treated group. The results presented in this report indicate that the antileukaemic activity of TNF-α is governed at least in part by the nature of the N-terminal amino acids