Targeting tumors with nonreplicating Toxoplasma gondii uracil auxotroph vaccines.
Toxoplasma gondii is an intracellular parasite that has evolved to actively control its invaded host cells. Toxoplasma triggers then actively regulates host innate interleukin-12 (IL-12) and interferon-γ (IFN-γ) responses that elicit T cell control of infection. A live, nonreplicating avirulent uracil auxotroph vaccine strain (cps) of Toxoplasma triggers novel innate immune responses that stimulate amplified CD8(+) T cell responses and life-long immunity in vaccinated mice. Here, we review recent reports showing that intratumoral treatment with cps activated immune-mediated regression of established solid tumors in mice. We speculate that a better understanding of host-parasite interaction at the molecular level and applying improved genetic models based on Δku80 Toxoplasma strains will stimulate development of highly effective immunotherapeutic cancer vaccine strategies using engineered uracil auxotrophs.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, 1 Medical Center Drive, Lebanon, NH 03756, USA.
Barbara A
BA
Fox
Kiah L
KL
Sanders
Shan
S
Chen
David J
DJ
Bzik
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use; D007113:Immunity, Innate / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000628:therapy*; D016052:Protozoan Vaccines / Q000627:therapeutic use*; D014122:Toxoplasma / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000627:therapeutic use
D019496:Cancer Vaccines; D016052:Protozoan Vaccines; D014613:Vaccines, Attenuated
CD8(+) T cells; IL-12p70; Toxoplasma gondii; avirulent uracil auxotrophs; immunotherapy; tumor regression