Biochemical properties and immunogenicity of L-phenylalanine ammonia-lyase: effects on tumor-bearing mice.
L-Phenylalanine ammonia-lyase (PAL) from yeast was used to deplete plasma L-phenylalanine and L-tyrosine in an attempt to achieve inhibition of tumor growth in mice. Plasma L-phenylalanine and L-tyrosine were reduced to nondetectable levels when circulating PAL activity was maintained at greater than or equal to 0.06 unit/ml. Repeated administration resulted in the appearance of anti-PAL antibodies. A radioimmunoassay based on the method of Farr was developed to determine quantitatively the presence of anti-PAL. Sublethal total-body irradiation temporarily suppressed the immunologic response of the host. Long-term specific immunosuppression to PAL was achieved with cyclophosphamide (CPA). A single dose of 180 mg/kg of CPA administered ip to mice 24 hours before, simultaneously with, or 24 hours after 100 units/kg of PAL induced tolerance for 450 days (20 injections of enzyme). The plasma half-life of PAL in CPA-treated mice remained essentially the same as that found after a single injection (25 hours), and anti-PAL probably will require specific immunosuppression of the host to repeated injections of the enzyme.
D000642:Ammonia-Lyases / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D007165:Immunosuppression Therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D010649:Phenylalanine / Q000097:blood; D010650:Phenylalanine Ammonia-Lyase / Q000097:blood / Q000276:immunology / Q000494:pharmacology*; D014443:Tyrosine / Q000097:blood
D014443:Tyrosine; D010649:Phenylalanine; D003520:Cyclophosphamide; D000642:Ammonia-Lyases; D010650:Phenylalanine Ammonia-Lyase