eBook: Advances in Cancer Immunology Research - 52

Cell therapy in 3D
The potential for the use of 3D models extends far
beyond small molecule drug screening. In addition
to 3D spheroids derived from cell culture, patient-derived
organoids from cancer biopsies can also be
used as a more personalized approach to the investigations
of possible therapies. As evidenced by a
multitude of publications, these models can also be
used to research cell therapies where a patient's immune
cells are reprogrammed to attack cancer cells.
In one example, PDOs were generated from colorectal
cancer (CRC) biopsies to investigate the potential
of bispecific antibody treatment. Researchers were
able to redirect T cell killing independently of their
T cell receptor specificity, using a bispecific antibody
that recognizes both CD3 and carcinoembryonic antigens
(CEA). The authors of this study were able to
demonstrate that those PDOs with high levels of CEA
expression were highly sensitive to treatment, while
those with low expression of CEA were resistant.
(Gonzalez-Exposito, et al 2019). CEA is expressed on
the surface of many colorectal cancers, making this
bispecific antibody therapy very promising.
A standardized method high-throughput
imaging and analysis of tumor
spheroids
3D cell culture models offer substantial promise for
future oncology research. It is now clearly demonstrated
that in terms of gene expression, responses
to treatment, and other characteristics, 3D culture
more closely resembles the in vivo characteristics of
cancer compared to 2D monolayers. Using the CeliFigure
5. Diagram of the PDO and allogeneic CD8 T cell co-culture model for studying drug resistance and sensitivity to T cell
bispecific antibody Cibisatamab. PDOs from multidrug-resistant metastatic CRCs were established and categorized based on
CEA cell-surface expression. PDOs were co-cultured with allogeneic CD8 T cells to assess sensitivity to cibisatamab immunotherapy.
(Gonzalez-Exposito, et al, 2019).
52

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