Table 2 Predicting the translation of... | American Society of Hematology

Table 2

Predicting the translation of preclinical therapeutic strategies

Will a new therapeutic strategy translate into the clinic?
1. Is the pathway in question still active in patients (or animals) receiving immune suppression? If not, does preclinical evidence suggest the inhibition of the pathway in isolation will be feasible and more efficacious than current immune suppression?
2. Is the effect large (complete) rather than incremental (partial)?
3. Does the intervention inhibit GVHD at multiple stages of its pathophysiology, and preferably early?
4. Is the pathway active in both class I– and class II–dependent GVHD? If not, it should at least not have opposing effects in CD8 and CD4 T-cell–dependent GVHD.
5. Are there potential toxicities in humans that might reasonably not be evident in the animal model?
6. Are there detrimental effects of the intervention on GVL and pathogenic-specific immunity and if so is this manageable and outweighed by the potential benefits in treating GVHD?
7. Bearing in mind that pharmaceutical companies have minimal interest in BMT as a sole market, is the pathway operative in other disease settings such that the generation and development of reagents to the clinic is likely to be commercially viable?

Will a new therapeutic strategy translate into the clinic?
1. Is the pathway in question still active in patients (or animals) receiving immune suppression? If not, does preclinical evidence suggest the inhibition of the pathway in isolation will be feasible and more efficacious than current immune suppression?
2. Is the effect large (complete) rather than incremental (partial)?
3. Does the intervention inhibit GVHD at multiple stages of its pathophysiology, and preferably early?
4. Is the pathway active in both class I– and class II–dependent GVHD? If not, it should at least not have opposing effects in CD8 and CD4 T-cell–dependent GVHD.
5. Are there potential toxicities in humans that might reasonably not be evident in the animal model?
6. Are there detrimental effects of the intervention on GVL and pathogenic-specific immunity and if so is this manageable and outweighed by the potential benefits in treating GVHD?
7. Bearing in mind that pharmaceutical companies have minimal interest in BMT as a sole market, is the pathway operative in other disease settings such that the generation and development of reagents to the clinic is likely to be commercially viable?