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. 2021 Apr 19;12:660916. doi: 10.3389/fimmu.2021.660916

Table 1.

Immune-modulatory drugs that may improve TB therapy.

Drug HDT Class Host Target Applications Preclinical data in TB Ref.
Doxycycline MMP Inhibitors Multiple MMPs Bacterial infections Improved TB containment in cells, guinea pigs; Phase II trial ongoing (NCT02774993) (11)
Marimastat MMP Inhibitors Multiple (MMP-1, -2, -7, -9, -14) Cancer (discontinued) Improved TB containment in mice (12, 13)
Andecaliximab MMP Inhibitors MMP-9 Cancer, auto-inflammatory disorders (in development) Reduced relapse rates in mice (14, 15)
Cipemastat MMP Inhibitors MMP-1, -8, -13 Rheumatoid arthritis (discontinued) Increased lung damage and death in mice; no effect in rabbits (16, 17)
Etanercept TNF antagonists TNFα Arthritis (various forms), ankylosing spondylitis Accelerated bacterial clearance, reduced relapse rates in mice; may improve outcome in TB-HIV patients (Phase I) or severely ill TB patients; risk of impaired bacterial containment without adequate anti-TB therapy (15, 1822)
Dexamethasone/Prednisolone Corticosteroids Broad-spectrum anti-inflammatory effects via modulation of glucocorticoid/mineralocorticoid receptor signaling Inflammatory and immune-mediated disorders (numerous) Modest improvements in lung function; recommended for TB meningitis (survival benefit) but not for pulmonary TB (2331)
Talazoparib PARP inhibitors PARP1/2; PARP3, PARP4, TNKS1, TNKS2 Cancer May reduce inflammation and TB lung damage in mice (3236)
Olaparib PARP inhibitors PARP1/2; PARP3, PARP4, PARP16, TNKS1, TNKS2 Cancer N/A (33, 34, 36)
Rucaparib PARP inhibitors PARP1/2, PARP3, PARP10, TNKS1, TNKS2 Cancer N/A (33, 34, 36)
Niraparib PARP inhibitors PARP1/2, PARP3, PARP4, PARP12 Cancer N/A (33, 34, 36)
Metformin MDSCs HIF1α, CD39, CD73, AMPK-DACHi-CXCL1 Diabetes Reduced severity and mortality in diabetic patients (37, 38)
Tasquinamod MDSCs S100A9 Cancer Decreased lung and spleen bacillary burden in mice (39)
ATRA MDSCs Upregulates glutathione synthase Cancer Decreased lung bacillary burden and pathology in mice and rats (4042)
DABIL-4 MDSCs IL-4R Preclinical model of breast cancer Decreased lung bacillary burden in mice (43)
Sildenafil MDSCs PDE-5i Erectile dysfunction and pulmonary hypertension Reduced lung bacillary burden, pathology and severity in mice (44)
Roflumilast and CC-11052 MDSCs PDE-4i COPD Improved lung function in mice (45, 46)
Denileukin Diftitox (Ontak®) Tregs IL-2R Refractory cutaneous T-cell lymphoma Reduced lung bacillary burden in mice (47)
Checkpoint blockade therapy Tregs CTLA4, PD1 Cancer Mtb-infected macaques overexpress CTLA-4 (48)
Curcumin M2 macrophages IL-10 Preclinical models of cancer Modest efficacy in mice (49)
Anti-IL-10 antibody Tregs IL-10 Preclinical model of cancer Reduced lung bacillary burden in mice (50)

MMP, matrix metalloproteinases; TNKS, tankyrase; PDE, phosphodiesterase.