Human malignant neoplasms not infrequently reveal mononuclear cell infiltrates which have features in common with immune-associated inflammatory reactions (Underwood, 1974). Although there is limited evidence for tumourrelated functional activity in the infiltrating leucocyte compartment (see Haskill, 1983), the relationship of the phenomenon at a functional or histological level to biological behaviour remains largely obscure.The majority of solid human neoplasms are characterised by marked cellular heterogeneity and any provisional assignment of in situ function will require the elucidation of the heterogeneity and microanatomical distribution of potential leucocytic effector cells relative to the tumour population. Such an analysis must also extend to the neoplastic *Present address:

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Palmitoyl derivatives of interferon alpha2b (p-IFNalpha) were prepared by covalent attachment of the fatty acid to lysine residues in the protein through a reaction with N-hydroxysuccinimide palmitate ester. The p-IFNalpha was characterized by capillary electrophoresis (CE), mass spectrometry (MS), SDS-PAGE, and antiviral assay. Flow-through diffusion cells and human breast skins were used to measure cutaneous and percutaneous absorption. Formation of p-IFNalpha derivatives was demonstrated by CE to be dependent on reaction time and reagent: protein ratio. Electrospray MS of the crude p-IFNalpha mixture indicated three populations of IFNalpha derivatives with 10, 11, and 12 palmitoyl substitutions. The addition of palmitoyl residues to IFNalpha under the conditions described reduced the antiviral specific activity by 50%. However, the cutaneous absorption of p-IFNalpha was about 5-6 times greater than the parent protein. The amount of p-IFNalpha and IFN alpha in whole skin after 24 h of treatment was 2.106 +/- 1.216 microg/cm2 and 0.407 +/- 0.108 microg/cm2, respectively. Approximately two times higher flux was detected for p-IFNalpha compared to the nonfatty acylated IFNalpha. The total amount of drug diffused in 24 h was also approximately two times higher for the p-IFNalpha. The results indicate a potential for using fatty acylated derivatives of IFN alpha for dermal and transdermal delivery.

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