Novel biology-driven strategies for SR-GVHD
| Approach . | Mechanism . | Clinical responses, % . | References . |
|---|---|---|---|
| Modification of alloreactive T cells | |||
| Anti-CD3/CD7 antibody conjugated to ricin toxin | Apoptosis↑ in T and NK cells | ORR, 60; CR, 50 | 136 |
| Brentuximab vedotin | CD30 inhibition, central memory ↓ (CD8+CD45RO+CD62L+ T cells) | ORR, 38.2 at day 28 | 139,140 |
| Vedolizumab | Integrin α4β7 inhibition, donor T-cell homing to GI tract↓ | ORR, 100 | 142 |
| ORR, 79 | 176 | ||
| ORR, 64 | 143 | ||
| Cytokines | |||
| Tocilizumab | IL-6 signaling↓ (Innate/adaptive response↓) | ORR, 67 | 147 |
| ORR, 44 | 146 | ||
| CR, 62.5 | 145 | ||
| F-652 (IL-22 dimer/Fc fusion molecule) | Preserved ISCs | NCT02406651* | |
| Gut regeneration↑ | |||
| Combination | |||
| Ruxolitinib | JAK1/2 inhibition | ORR, 81.5 | 85 |
| ORR, 45 | 177 | ||
| ORR, 57 | 152 | ||
| ORR, 78 | 178 | ||
| ORR, 84 | 153 | ||
| Tissue regeneration | |||
| Lithium | Wnt signaling ↑ by inhibiting GSK3 | CR, 50 | 157 |
| AAT | Serine protease inhibitor, ↑ Treg, | ORR, 66.7 | 163 |
| ↓APC function | |||
| ↓Proinflammatory cytokines (IL-6) | ORR, 65 | 162 | |
| Microbiome | |||
| FMT | Gut microbiome diversity ↑ | ORR, 100 | 99 |
| ORR, 75 | 101 | ||
| Resistant starch | Modification of metabolome | NCT02763033,* NCT02805075* |
| Approach . | Mechanism . | Clinical responses, % . | References . |
|---|---|---|---|
| Modification of alloreactive T cells | |||
| Anti-CD3/CD7 antibody conjugated to ricin toxin | Apoptosis↑ in T and NK cells | ORR, 60; CR, 50 | 136 |
| Brentuximab vedotin | CD30 inhibition, central memory ↓ (CD8+CD45RO+CD62L+ T cells) | ORR, 38.2 at day 28 | 139,140 |
| Vedolizumab | Integrin α4β7 inhibition, donor T-cell homing to GI tract↓ | ORR, 100 | 142 |
| ORR, 79 | 176 | ||
| ORR, 64 | 143 | ||
| Cytokines | |||
| Tocilizumab | IL-6 signaling↓ (Innate/adaptive response↓) | ORR, 67 | 147 |
| ORR, 44 | 146 | ||
| CR, 62.5 | 145 | ||
| F-652 (IL-22 dimer/Fc fusion molecule) | Preserved ISCs | NCT02406651* | |
| Gut regeneration↑ | |||
| Combination | |||
| Ruxolitinib | JAK1/2 inhibition | ORR, 81.5 | 85 |
| ORR, 45 | 177 | ||
| ORR, 57 | 152 | ||
| ORR, 78 | 178 | ||
| ORR, 84 | 153 | ||
| Tissue regeneration | |||
| Lithium | Wnt signaling ↑ by inhibiting GSK3 | CR, 50 | 157 |
| AAT | Serine protease inhibitor, ↑ Treg, | ORR, 66.7 | 163 |
| ↓APC function | |||
| ↓Proinflammatory cytokines (IL-6) | ORR, 65 | 162 | |
| Microbiome | |||
| FMT | Gut microbiome diversity ↑ | ORR, 100 | 99 |
| ORR, 75 | 101 | ||
| Resistant starch | Modification of metabolome | NCT02763033,* NCT02805075* |
↓, decrease; ↑, increase; AAT, α-1-antitrypsin; CR, complete response; FMT, fecal microbiome transplantation; GSK3, glycogen synthase kinase 3; ORR, overall response rate; VGPR, very good partial response.
Clinical trial number.