Background
The use of CAR-T cells (chimeric antigen receptor T cells) has shown promising success in the treatment of B hematological malignancies, but their therapeutic performance in solid tumors remains more limited. Our objective is to decipher the dynamics of CAR-T cells in solid tumors in vivo at the single-cell level and to compare it to hematological tumor models to identify limitations to CAR-T cells efficacy.
Materials and Methods
For this purpose, we developed a murine subcutaneous solid tumor model to study the effect of CAR-T cells therapy. We generated tumor cell lines expressing a fluorescent probe to monitor apoptosis (the DEVD probe) and expressing the CD19 antigen. Response to CAR-T cells is then analyzed by flow cytometry and intravital imaging.
Results
We found that CAR-T cells therapy in this solid tumor model prolong mouse survival and delay tumor growth but could not induce complete remission. Moreover, we could visualize CAR-T cells infiltration at the tumor site. Therefore, our model is suitable to visualize potential limitations of CAR-T cells therapy. We are currently using intravital two-photon imaging to decipher CAR-T cells behavior and killing potential during the course of CAR-T cells therapy.
Conclusions
In sum, we have established a new model suitable for intravital imaging that will help identify limitations of CAR-T cells activity in the context of a solid tumor.
B. Arnaud: None. M. Ruggiu: None. Z. Garcia: None. F. Lemaître: None. C. Grandjean: None. P. Bousso: None.