Effect of “Methotrexate” and “Melphalan” on the Survival of Tumour and Skin Homo-grafts

Abstract

SEMI-ISOLOGOUS (F1 hybrid) mice surviving systemic leukaemia L1210 after extensive therapy with halogenated derivatives of ‘Methotrexate’ (MTX) were shown to be immune to re-inoculation with sensitive or resistant sub-lines of leukaemia L12101–3. In other work4–6, it was observed that MTX therapy of mice bearing homografts of MTX-resistant leukaemias abrogated the immune response. However, in a system involving differences at the strong H-2 histocompatibility locus, pretreatment of mice with MTX failed to promote the growth of L12107. In the latter system, pretreatment with a number of alkylating agents (cyclophosphamide, triethylene melamine, and ‘Melphalan’) and X-irradiation resulted in marked immune suppression. In view of the foregoing results, and the observation that MTX therapy did not interfere appreciably with the ability of an inoculum of splenic tissue to render mice immune to L12105, we decided to determine what effect a dose-level of MTX capable of abrogating the immune response to tumour homograft would have on the survival of skin homografts. Also, as part of the same experiment, the effect of pro-treatment with MTX on the immune response to skin and tumour homografts was determined, since, in the present system, only minor histocompatibility differences were involved. ‘Melphalan’, a potent immune suppressor7, was used as a positive control.