Page 120 - Bio Engineering Approaches to Cancer Diagnosis and Treatment

118 CHAPTER 5 Cell therapy

Table 5.1 Characteristic of CAR T cells and TCR T cells [10].
CAR T cells TCR cells
Signal amplification from synthetic biology: Sensitive signal amplification derived by
200 targets can trigger CAR T cells evolution of the TCR
Avidity-controllable Low-avidity, unless engineered
CAR T cells targets surface structures: TCR cells targets intracellular proteome
proteins, glycan
MHC-independent recognition of tumor targets Requires MHC class I expression and
HLA matching on tumor
Decade-long persistence Lifelong persistence
Serial killers of tumor cells Serial killers of tumor cells
Cytokine release syndrome more severe than Off-tumor toxicity difficult to predict
TCR-based therapy

Due to the high costimulatory of CAR T cells, it has enabled the persistent cells
in cell therapy treatment to be one of the aims of CAR T cell therapy. The result of
treatment with CAR T cells was disappointing until 2011 as the peripheral-blood T
cell engineered with a CD19 was prepared and infused as a specific CAR T cell to
destroy the lymphomas and leukemia in mice. Its positive result was promising for
treatment using CAR T cell therapy [2]. The success of using CD19 CAR T cells
has been observed in other leukemia and hematological malignancies. In 2018, Park
et al. studied 53 patients who got anti-CD19-CAR T cells as a treatment for more
than one year [15]. The result has indicated that 83% of the patient got complete
remission in the median 29 months of follow up. Recently, a powerful antitumor
activity using CAR T cell targeting CD22 in all hematological malignances and
BCMA in myeloma have been reported. But all those have restriction to the B cell
lineage that it causes toxicity because of the normal cell targeting. And until now tar-
geting only tumor-associated antigens, remain limited. However, the combination of
chemotherapy with CAR T cells could be promising, in particular for the patient with
chemotherapy-refractory [15]. In 2015 Koshenderfer et al. have shown the effect
of the treating chemotherapy-refractory-cell malignancies with anti-CD19 CAR T
cells [16]. In this clinical trial research, 15 patients with advanced B-cell malignan-
cies were investigated. They have received a conditioning chemotherapy regimen of
cyclophosamide and fludarbine and single infusion of anti-CD 19 CAR T cells. The
result has shown that eight patients got complete remission and four of them got par-
tial remission. Also acute toxicity has been observed (fever, hypotension, delirium)
but the result was anticipant. But it still needs further research and investigation in
order to be set as a treatment method [16].
In general, one limitation of ACT is delivering targeted lymphocyte to tumor
sites and sometimes its problem in expansion in the immunosuppressive tumor
microenvironment [16]. In order to reduce and solve this problem using biomedical
engineering, scientists have prepared a scaffold with alginate to implant it close or
at resection sites [17].