Repeated immunization with plasmid DNA formulated in poly(lactide-co-glycolide) microparticles is well tolerated and stimulates durable T cell responses to the tumor-associated antigen cytochrome P450 1B1

• Published in: Clinical immunology (Orlando, Fla.) Vol. 112; no. 1; pp. 45 - 53
• Main Authors: Luby, Thomas M, Cole, Geoffrey, Baker, Lisa, Kornher, J.Steven, Ramstedt, Urban, Hedley, Mary Lynne
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-07-2004; Elsevier
• Subjects: Animals; Aryl Hydrocarbon Hydroxylases; Biological and medical sciences; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; Cancer Vaccines - genetics; Cancer Vaccines - immunology; CD8+ T cell response; CD8-Positive T-Lymphocytes - immunology; Cytochrome P-450 CYP1B1; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - immunology; Cytochrome P450 CYP1B1; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Glycolates - pharmacology; HLA-A2 Antigen - immunology; Immunization - methods; Immunopathology; Lactic Acid; Lymphocyte Activation - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microspheres; Plasmid DNA; Poly(lactide-co-glycolide) microparticles; Polyglycolic Acid; Rats; Rats, Sprague-Dawley; Repeated immunization; Toxicity Tests; Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Repeated immunization; Cytochrome P450 CYP1B1; Plasmid DNA; Poly(lactide-co-glycolide) microparticles; CD8+ T cell response; Immunopathology; Immunization; Immune response; Tumor associated antigen; Repeated sequence; Cytochrome P450; Plasmid; Immunology; EC 1.14.14.1; DNA; Microparticle
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2004.04.002

Injection of microparticle-encapsulated DNA elicits immune responses to plasmid-encoded antigens in mice and humans. Cytochrome P450 CYP1B1 (CYP1B1) is a member of the CYP1 P450 enzyme family that is overexpressed in a variety of solid tumors. The work described herein was performed to study the kinetics of stimulating T cell responsiveness with an encapsulated DNA encoding CYP1B1 and provides support for the clinical development of this formulation. Immunization of HLA-A2/K
b transgenic mice with human CYP1B1 encoding plasmid DNA formulated in poly(lactide-co-glycolide) (PLG) microparticles elicits CD8+ T cells that respond to human CYP1B1-positive target cells. The duration of the immune response, the effect on the immune response of multiple injections, and the safety of repeated injections were studied. These results show that the PLG-encapsulated DNA therapeutic elicits durable immune responses to CYP1B1, the responses are dependent on repeat immunization, and that the formulation is well tolerated.