Table 4 Current strategies to ameliorate immune response upon transplantation of allogeneic cellular derivatives.
From: Immunological considerations and challenges for regenerative cellular therapies
Strategy | Principle | Limitations | References |
|---|---|---|---|
Immunosuppression | Use of drugs targeting essential pathways for immune cell performance. | – Cytotoxic effects– Vulnerable recipient’s immune system | |
| Types: glucocorticoids/steroids, cytostatics, specific antibodies, drugs acting on immunophilins/other mechanisms | ||
HLA matching | HLA-typed cell banks that allow the matching of donor and recipient cells using homozygous cell lines with frequent HLA haplotypes. | – Minor alleles not matched – Might require immunosuppression | |
| Examples: United Kingdom, Japan | ||
Genetically modified Cells | Genetically engineered cells with gene editing techniques (e.g., CRISPR/Cas9, TALENS) that would bypass specific immune mechanisms of action. | – Safety concerns: | |
| • Off-target effects of targeting | ||
Examples: HLA-I or/and -II knock out cell lines, HLA-C retained lines, immune cloaked cells | • Conversion to malignant/infected cell that will not be recognized | ||
Immune Tolerance | A combination of deletion, cell-intrinsic checkpoints, and suppression by regulatory mechanisms. | – Specificity of the inhibitory drug (costimulatory and adhesion blockade) | |
| Examples: costimulatory and adhesion blockade, inhibitory ligand overexpression, adoptive cell therapy with naturally occurring Tregs/induced donor-specific Tregs | – Genetic engineering/viral off-targets (ligand overexpression) | |
– Cost and infrastructure needed per patient (adoptive therapy) | |||
Cell Shielding | Protection or shielding of the derived cells with specific materials or encapsulation devices | – Immunocompatible materials | |
– Vascularization and function of the cells | |||
| Examples: alginate-beads, functionalized hydrogels | – Permeability to essential soluble factors | |
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