The Johnson Lab

IDO and Complement in Tumor Immunology

The goals of this project are: (i) to test the guiding hypothesis that IDO acts as a crucial modulator of therapy-induced inflammation in solid tumors, by inhibiting production of pro-inflammatory cytokines and suppressing activation of complement, and (ii) to elucidate the fundamental molecular mechanisms by which adding an IDO-blocking drug to conventional chemo-radiotherapy elicits synergistic effects on survival and changes the nature of the tumor response.

IDO-Based Immunotherapy for Brain Tumors

The goal of this grant is to use animal models to test the hypothesis that IDO is a critical vascular quiescence factor in brain tumor biology and that blocking IDO allows standard chemo-radiation therapy to trigger vascular activation and innate inflammatory pathways leading to rapid microangiopathic tumor destruction.

Phase I trial of indoximod in combination with temozolomide-based therapy for children with progressive primary brain tumors

The primary goal of this clinical trial is to test the hypothesis that adding indoximod (IDO-blockade) to standard temozolomide therapy is safe and tolerable in children with relapsed brain tumors, and that this combination immuno-chemotherapy will show preliminary evidence of synergistic efficacy. Translational clinical trials developed as a results of research in the Johnson Laboratory include:

• A phase I/II study of the combination of indoximod and temozolomide for adult patients with temozolomide-refractory primary malignant brain tumors
  • (PI: Mott; Co-I: Johnson, NCT02052648, open to accrual for patients 16 years and older with glioblastoma)
• Phase I trial of indoximod in combination with temozolomide-based therapy for children with progressive primary brain tumors
  • (PI: Johnson, IND amendment pending at FDA, anticipated to open mid-2015 for children age 3-18 years with relapsed or progressive brain tumors)