CAR T cells expressing a bacterial virulence factor trigger potent bystander antitumour responses in solid cancers

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Jin, Chuan,1986-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi (author)

Chimeric antigen receptor T cells (CAR T cells) are effective against haematologic malignancies. However, in solid tumours, their potency is hampered by local immunosuppression and by the heterogeneous expression of the antigen that the CAR targets. Here we show that CAR T cells expressing a pluripotent pro-inflammatory neutrophil-activating protein (NAP) from Helicobacter pylori trigger endogenous bystander T-cell responses against solid cancers. In mice with subcutaneous murine pancreatic ductal adenocarcinomas, neuroblastomas or colon carcinomas, CAR(NAP) T cells led to slower tumour growth and higher survival rates than conventional mouse CAR T cells, regardless of target antigen, tumour type and host haplotype. In tumours with heterogeneous antigen expression, NAP secretion induced the formation of an immunologically 'hot' microenvironment that supported dendritic cell maturation and bystander responses, as indicated by epitope spreading and infiltration of cytotoxic CD8(+) T cells targeting tumour-associated antigens other than the CAR-targeted antigen. CAR T cells armed with NAP neither increased off-tumour toxicity nor hampered the efficacy of CAR T cells, and hence may have advantageous translational potential. T cells expressing a pluripotent pro-inflammatory neutrophil-activating protein from Helicobacter pylori trigger endogenous bystander T-cell responses against solid cancers.

Ma, JingUppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)jinma809 (author)
Ramachandran, Mohanraj,1988-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Vaskulärbiologi(Swepub:uu)mohra272 (author)
Yu, Di,1985-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi(Swepub:uu)diayu422 (author)
Essand, MagnusUppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi(Swepub:uu)magnessa (author)
Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

By the author/editor: Jin, Chuan, 1986 ...; Ma, Jing; Ramachandran, Mo ...; Yu, Di, 1985-; Essand, Magnus

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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