Cellular therapeutic potential of genetically engineered stem cells in cancer treatment

Figures & data

Figure 1. Phases of carcinogenesis – a process where a cell progresses from the preneoplastic cell into tumour cell and in situ carcinoma, leading to the invasion of blood vessels and lymph nodes, as well as surrounding tissue (Delpu et al., 2013).

Figure 2. Gene therapy in cancer treatment achieved by the use of tumour-specific promoter (TSP), altering the expression of genes specifically involved in cancer cell development, preventing tumorigenesis (Chen et al., 2018).

Figure 3. A scheme illustrating the plasticity of cancer cell phenotypes, their main characteristics and signalling pathways that can contribute to cancer stem cell development, as well as environmental factors (synthesis of interleukins, oxygen radicals and growth factors) (Kabakov et al., 2020).

Figure 4. Tumor niche contains tumour cells, cancer stem cells, different immune cells (T-cells, dendritic cells, macrophages, etc.) and their products - chemoattractants, which have the main role in process of carcinogenesis (Chu et al., 2020).

Figure 5. Possible applications of stem cell therapy in oncology; (1) Transplantation of HSC after chemotherapy and radiotherapy for the regeneration of blood marrow cells and leukocytes, (2) the use of ESCs and iPscs for the development of vaccines against cancer and (3) the use of MSCs for the transportation of genes and drugs to targeted tumour environment (Chu et al., 2020).

Table 1. Clinical trials focused on the efficacy of MSCs in decreasing the onset of GVDH occurrence, induced by allogeneic HSC transplantation in cancer patients.

Diseases and interventions	Phase	Outcome	Reference
Recent published/completed trials
Refractory chronic GVHD- Adipose tissue-MSC (1–3 × 10^6/kg) and ciclosporin, prednisone.	I/II	71.4% of patients live, 80% of patients achieved complete remission (CR). 100% of patients were steroid-free at week 56. There are no side effects associated with MSC treatment.	(Muroi et al., 2016)
Steroid-refractory stage III or IV acute GVHD- 72–100 × 10^6 MSC.	II/III	At 24 weeks (primary endpoint), 12/25 (48%) patients achieved a CR. At 52 weeks, 48% of patients receiving MSCs were alive.	(F. Yin et al., 2014)
Refractory acute GVHD. MSC bone marrow (2 × 10^6cells/kg), 3 doses per week.	I	5/7 patients achieved CR with a significant reduction in inflammatory cytokines. Good correlation between clinical responses with reduction in biomarker levels (Elafin, CK18 and Reg 3α).	(Baron et al., 2010)
Infusion of mesenchymal stem cells on the same day as hematopoietic stem cell infusion, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine.	II	After 100 days (primary endpoint), <35% non-relapse mortality (NRM) 19/20 patients achieved permanentHSC engraftment.	(Zhou et al., 2010)
Sclerodermatous GVHD- bone marrow MSC (10–20 × 10^6 cells, infusion into the anterosuperior iliac spine).	I	Reduce symptoms in all 4 patients. Dramatic increase in Th1/Th2 cell ratio. No side effects.	(Wei et al., 2018)

Table 2. Presentation of clinical research investigating the effects of stem cell therapy in cancer treatment.

Stem cell therapy	Drug(s)	Tumour type	Phase	Trial number	Reference
NSCs expressing CD	5-FC	Recurrent high-grade gliomas	Phase I, completed	NCT01172964	(von Einem et al., 2019)
NSCs expressing CD	5-FC and leucovorin	Recurrent high-grade gliomas	Phase I, ongoing	NCT02015819	(von Einem et al., 2019)
MSCs expressing HSV-TK	Ganciclovir	Advanced, recurrent or metastatic gastrointestinal adenocarcinoma	Phase I/II, completed	EudraCT 2012–003741–15	(Sage et al., 2018)
MSCs expressing TRAIL	-	Lung adenocarcinoma	Phase I/II,	NCT03298763	(Rosenblum et al., 2018)

Figure 6. Engineered extracellular vesicles (EVs) for delivering therapeutic entities by the process of exogenous loading after their isolation or endogenous loading during EVs biogenesis, protecting them from damage and increasing the success of therapy (Yin, L. Liu et al., 2020).

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