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Lunch & Poster Display session

37P - Chemokine receptor CCR2b expressing anti-Tn-MUC1 CAR-T cells enhanced anti-breast cancer activity

Date

12 Dec 2019

Session

Lunch & Poster Display session

Presenters

Yiguang Lin

Citation

Annals of Oncology (2019) 30 (suppl_11): xi12-xi15. 10.1093/annonc/mdz448

Authors

Y. Lin1, H. Yin2, H. An2, C. Zhou2, L. Zhou2, S. Chen1, E. McGowan1

Author affiliations

  • 1 -, The First Affiliated Hospital of Guangdong Pharmaceutical University, 510080 - Guangzhou/CN
  • 2 -, Guangzhou Anjie Biomedical Technology Co. Ltd, Guangzhou/CN
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Resources

Abstract 37P

Background

Enhanced anti-tumour activity is required for eradication of solid tumours by CART cells. One possibility of enhancing anti-tumour activity is by programming CART cells to express chemokine receptors that match chemokines produced either by the tumours or tumour-associated cells, thereby improving the infiltrating capacity of the CART cells. In this study, we engineered CCR2b expressing anti-Tn-MUC1 CAR T cells for the treatment of breast cancer.

Methods

Anti-Tn-MUC1-CARs were constructed using the SM3 scFv. Following lenti-MUC1 CAR retroviral transduction, efficiency of transgenic expression was assessed by flow cytometry. CCR2b expressing anti-Tn-MUC1 CAR T cells were prepared using PLV-CAR-5E5-CCR2b lentivirus. The susceptibility of MCF-7 cells to either anti-MUC1 CART or CCR2b expressing anti-MUC1 CART cell-mediated lysis was assessed using in vitro killing assays. For cytolytic analysis, CART-cells were cocultured 10:1 (effector:target) ratio with MCF-7 cells. The effects of CCR2b expressing CART cells on anti-tumour activity and infiltration were also assessed in an in vivo murine xenograft model.

Results

Activated T cells co-modified with both CCR2b and anti-MUC1-CAR had greater anti-tumour activity both in vivo and in vitro. When the effector / target cell ratio was 10, the killing rates of CART and CART-CCR2b were 56.9% and 83.9%, respectively. Tumour size was significantly smaller (P < 0.001) in the CAR-CCR2b group compared to the CAR alone group. At day 7 post-injection of CART cells, the infiltrated T cells was significantly increased (∼2 folds) in the CAR-CCR2b group compared with the CART only group.

Conclusion

Our data demonstrated that the anti-tumour activity of the CCR2b expressing anti-Tn-MUC1 CART cells is 1.5 times more potent than CART cells without CCR2b. Augmentation of tumour suppression was also demonstrated in vivo in a murine xenograft model. These pre-clinical results show translational potential to the clinic for treatment of solid breast tumours.

Clinical trial identification

Editorial acknowledgement

Not Applicable.

Legal entity responsible for the study

Guangzhou Anjie Biomedical Technology Co. Ltd.

Funding

Guangzhou Anjie Biomedical Technology Co. Ltd.

Disclosure

All authors have declared no conflicts of interest.

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