Targeting tumors with nonreplicating Toxoplasma gondii uracil auxotroph vaccines

Barbara A. Fox, Kiah L. Sanders, Shan Chen, and David J. Bzik Trends in Parasitology, 2013-09-01, Volume 29, Issue 9, Pages 431-437 Copyright © © 2013 Elsevier Ltd Highlights • Immunotherapy based on avirulent Toxoplasma reverses tumor-associated immune suppression. • Toxoplasma activates tumor-specific CD8 + T cell responses. • Toxoplasma immunotherapy regresses established solid tumors. 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 Δ ku80 Toxoplasma strains will stimulate development of highly effective immunotherapeutic cancer vaccine strategies using engineered uracil auxotrophs.