Table 4.
Summary of studies evaluating the role of costimulation blockade in VCA NHP models.
| References | Model | Tissue | Regimen | Graft survival | Cell population affected (mechanism) |
|---|---|---|---|---|---|
| PRECLINICAL STUDIES OF COSTIMULATION BLOCKADE IN VCA | |||||
| Atia et al. (93) | Monkey | Forearm | Belatacept + Steroids (3 groups: With ustekinumab, with secukinumab or without additional drugs) | Decreased (in all groups compared to historical control) | T cells (DSA formation prevention; decreased T cells, IL-17a T cells and IL-17a in ustekinumab and secukinumab treated animals) |
| Foster et al. (94) | Rat | Hindlimb | CTLA4-Ig + BM | Prolonged | T-cells (clonal expansion inhibition, mixed chimerism) |
| Freitas et al. (38) | Monkey | Forearm | CTLA4-Ig/Belatacept + Tacrolimus | Prolonged | T-cells (bimodal distribution of CD2lo and CD2hi CD8+ T cells, DSA formation prevention) |
| Iwasaki et al. (95) | Rat | Hindlimb | CTLA4-Ig | Prolonged | T-cells (mixed chimerism) |
| Larsen et al. (96) | Mouse | Skin | CTLA4-Ig + MR1(CD40 blockade) | Prolonged | T-cells (clonal expansion inhibition) |
| Lin et al. (92) | Rat | Skin | CTLA4-Ig + DST | Prolonged | Lymphocytes (50% reduced in vitro proliferative response) |
| Lin et al. (97) | Mouse | Hindlimb | CTLA4-Ig + anti-CD154 +RPM | Prolonged | T-cells (Increased Tregs, decreased CD4+, CD8+ counts) |
| Oh et al. (98) | Mouse | Hindlimb | CTLA4-Ig + anti-CD154 +TBI | Prolonged | T-cells(clonal deletion of donor-reactive T cell clones, mixed chimerism, Increased Tregs) |
| Schweizer et al. (99) | Rat | Hindlimb | Tacrolimus+CTLA4-Ig+ASC+ALS | Prolonged | T-cells (Increased Tregs, mixed chimerism) |
| Wachtman et al. (100) | Swine | Hindlimb | CTLA4-Ig+Tacrolimus | Prolonged | NR |
ALS, antilymphocyte serum; ASC, Adipose tissue derived stem cells; BM, Bone marrow; DSA, Donor specific antibodies; DST, Donor-specific cell (splenocyte) transfusion to graft recipient; MR1, Anti-CD40L mAb; NR, Not reported; RPM, Rapamycin TBI, Total body irradiation.