Table 1.
Leading Clinical and Preclinical candidates with potential to increase DCV efficacy. Definitions: DC gen - DC generation; DCV prod - DCV production; caTLR4 - constitutively active TLR4; shRNA - short hairpin RNA; siRNA - short interfering RNA; TKI - tyrosine kinase inhibitor.
| AuthorsRef | Preclinical/Clinical | DCV Stage | Target | Key Results | Applicable to Pediatrics |
|---|---|---|---|---|---|
| Nair, et al.17 | Preclinical | DC gen | New DC source | Feasible to create DC from cryopreserved autologous stem cell apheresis product | Yes |
| Benteyn, et al.53 | Preclinical | DCV prod | DC activation | In vivo DC maturation with proprietary co-stimulatory molecules – TriMix (CD40L, CD70, caTLR4) | Unknown |
| Olin, et al.35 | Clinical | DCV prod | Novel Antigen | DC loaded with allogeneic tumor cell line lysates were tolerated, best response SD in 1 patient | Likely |
| Van Nuffel, et al.52 | Clinical | DCV prod | DC activation | Durable T-cell and clinical response in chemorefractory melanoma patient treated with TriMix | Unknown |
| Mitchell, et al.50 | Clinical | Adjuvant | Effector T-cells | ↑ DC migration to draining lymph nodes, ↑ interferon- γ production post-vaccine, improved PFS | Yes |
| Rossowska, et al.61 | Preclinical | Immuno-modulation | IL-10 | Inhibition of IL-10 with DCV ↑ tumor growth inhibition in a murine model | Unknown |
| Ge, et al.58 | Preclinical | Immuno-modulation | PD-1/PD-L1 | PD-L1 blockade during DC generation/ injection ↓ tumor growth and ↑ PFS in murine breast cancer model | Likely |
| Wang, et al.60 | Preclinical | Immuno-modulation | PD-1/PD-L1 | Transduction of shRNA against PD-L1 into DC ↓ PD-L1 expression, ↓ IL-10 production, ↑ IL-12 | Unknown |
| Van der Waart, et al.59 | Preclinical | Immuno-modulation | PD-1/PD-L1 | siRNA silencing PD-L1 and L2 in DC ↑ in vitro T-cell priming and in vivo CD8+ T-cell responses | Unknown |
| Lowe, et al.69 | Preclinical | Immuno-modulation | Effector T-cells | TKI dasatinib combined with DCV ↓ tumor growth and ↑ OS compared to either modality alone | Likely |