Tissue Engineered Models of Brain Tumors and Their Applications

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pro-drug, tirapazamine, therapy was more effective in the core of the central

chamber where the development of hypoxia and necrotic core were located, as

outer layers were more oxygenated [174]. To translate into clinics, these drug

screening platforms can be manufactured as patient-on-chip systems by a com-

bination of scaffolds with patient-derived GBM cells which ultimately aim to

predict patient-specific prognosis and to choose the best course of treatment

unique to each patient [206].

3.4.3

Immunotherapy

Since the extensive information on the development and microenvironment

of tumors have been uncovered, these mechanisms are actively targeted to

eradicate tumor cells within the body. As explained above, tumor microenvi-

ronment has significant impact on the growth and metastasis of the tumors

especially by immunosuppression. Therefore, addressing to the possible routes

of the inference of immunosuppression and firing the immune reaction can be

benefited to achieve good prognosis. In this strategy, activation of immune

system and exploitation of the immune activity are harnessed in the cancer

immunotherapy as a potential alternative to traditional therapy to eliminate

tumors cells from the body as well as to prevent relapse [207]. For this pur-

pose, vaccines, oncolytic viruses, immune check-point blockade, and adoptive

cell transfer can be combined with primary treatments of chemo- and radio-

therapy to overcome the barrier of the cancer immunosuppression [208–210].

Currently, some of these strategies are under clinical trials for GBM [211, 212].

For these therapies, in vivo models are commonly investigated and further,

clues derived from in vitro GBM models have provided profitable data in the

area to discover therapeutic targets and engineered immune system cells [213].

As a recent evidence of promise of this approach, in clinical trials, genetically

engineered T cells (CAR-T) have been investigated to direct and amplify T

cell cytotoxicity towards GBM cells [214]. These T cells are engineered to carry

surface proteins that can recognize tumor antigens so that their tumor-killing

efficacy is improved. To achieve this, Jacob et al. co-cultured patient-derived

GBM organoids with anti-EGFRvIII CAR-T cells and, activated T cells se-

creted amplified levels of IL-2, IFN-γ, and TNF-α, they effectively killed tu-

mor cells upon antigen recognition and proliferated at the periphery of the

organoids [157]. Combinatorial application of this therapy also holds potential

for patient and tumor-infiltrating T cell survival, as B7H3-CAR-T cells com-

bined with IL-7 expressing oncolytic adenovirus provided promising activity

both in vitro and in vivo [215].

3.4.4

Response to Radiotherapy

In clinics, it is often impossible to remove whole tumor mass and outcome

remains to be poor, as unresected cancer cells continue to grow causing recur-

rence. This issue highlights the necessity and influence of chemotherapy and