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Poster session 14

759P - Preconditioning with irradiation enhances efficacy of B7-H3-CAR-T in treating solid tumor models

Date

10 Sep 2022

Session

Poster session 14

Topics

Tumour Immunology;  Targeted Therapy;  Immunotherapy

Tumour Site

Presenters

Tian Wang

Citation

Annals of Oncology (2022) 33 (suppl_7): S331-S355. 10.1016/annonc/annonc1058

Authors

T. Wang1, F. You2, Y. Li2, S. Xiang2, H. Wu2, H. Meng3, N. Yang4, B. Zhang5, L. Yang5

Author affiliations

  • 1 Clinical Research, PersonGen BioTherapeutics(Suzhou) Co., Ltd., 215000 - Suzhou/CN
  • 2 New Medicine Research, PersonGen BioTherapeutics(Suzhou) Co., Ltd., Suzhou/CN
  • 3 Clinical Research, PersonGen BioTherapeutics(Suzhou) Co., Ltd., Suzhou/CN
  • 4 Business Development, PersonGen BioTherapeutics(Suzhou) Co., Ltd., Suzhou/CN
  • 5 General Manager Office, PersonGen BioTherapeutics(Suzhou) Co., Ltd., 215000 - Suzhou/CN
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Abstract 759P

Background

Limited efficacy of CAR-T cells in treating solid tumors is largely due to the immunosuppression in the tumor microenvironment (TME). B7-H3 is expressed in most solid tumors including stromal fibroblasts and tumor blood vessels in TME. Radiotherapy has been found to alter TME in activating immuno-response, we tested and report the exploratory results of B7-H3-CAR-T in treating solid tumor models with preconditioning of radiotherapy.

Methods

A humanized B7-H3 scFv sequence CAR-T was constructed (named TAA06). TAA06 was prepared using CliniMACS Prodigy. Pharmacodynamics of TAA06 monotherapy was first assessed in vitro and in vivo. Whether local irradiation can improve TME and synergistically enhance the efficacy of CAR-T were then investigated.

Results

TAA06 monotherapy completely eradicated tumors in neuroblastoma and pancreatic tumor models, but it showed little effect on xenograft models derived from colorectal HCT-15 cells. Irradiation was found to increase expression levels of B7-H3 in HCT-15, PANC-1, AML-5 and U87-MG cell lines significantly, suggesting a possible synergistic enhancement effect of radiotherapy. Consequently, HCT-15 cells were selected to inoculate on both sides of mouse backs and developed the modeled animals; one side of mouse backs was pre-treated with irradiation before intravenous CAR-T cells injected. Tumor cells on the irradiated side were eradicated completely by CAR-T cells. Further pathological examination confirmed CAR-T cell infiltration in tumor tissues after irradiation, whereas CAR-T cell infiltration in non-irradiated tumor tissues was virtually absent.

Conclusions

This study demonstrated that pre-treatment with local irradiation significantly enhanced the ability of CAR-T to infiltrate and kill tumors. The efficacy of combination therapy to treat solid tumors in patients will have to be investigated.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

PersonGen BioTherapeutics(Suzhou) Co., Ltd.

Funding

PersonGen BioTherapeutics(Suzhou) Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.

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