Table 1.

Biological agents utilizing engineered mesenchymal stem cells (MSCs) as vehicle for ligand delivery and its safety. TRAIL—tumour necrosis factor-related apoptosis inducing ligand; CSCs—cancer stem cells; IFN— interferon; IL—interleukin.

Biological Agents	Mechanism	Tumour Model	Toxicity and Safety Concern	References
IL-2	Reduce and inhibit tumour growth dependent of natural killer (NK) cells	Renal cell carcinoma, glioma	May cause capillary leak syndrome and fluid accumulation	[53,54,79]
IL-12	Inhibit tumour growth dependent of NK cells	Melanoma model, renal cell carcinoma	Haematological toxicity, such as neutropenia and thrombocytopenia	[80,81,82]
IL-15	Abolished tumour growth dependent of NK and CD8+ T cells	Pancreatic tumour	Probability for autoimmune toxicity	[56,83]
IL-18	Suppress proliferation, migration, and invasion	Breast tumour	Haematological toxicity, hypotension, and bradycardia	[84,85]
IFN-β	Inhibit tumour growth and metastasis in vivo	Melanoma, breast tumour	Haematological-, autoimmune-, and hepato-toxicity	[44,55,86]
TRAIL	Induce apoptosis, inhibit clonogenicity and tumour bulk	Lung metastasis, lung CSCs, glioma, pancreatic cancer, mesothelioma,	Mild constitutional toxicity (e.g., nausea, fever, and constipation) and anaemia	[45,47,48,58,87]
Pro-drug converting enzymes	Inhibition of tumour growth in vitro and in vivo	Glioma, prostate cancer, osteosarcoma	“Off site” activated drug accumulation	[59,60,61,63]
Oncolytic virus	Oncolytic viruses mediated tumour regression in vivo	Glioblastoma, brain metastasis, leukemia and pancreatic cancer	Potential for virus mutation, normal cell toxicity, and human viral transmission	[71,78,88,89]