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BiTE-secreting T cells effectively target ovarian cancer and prolong antitumor immunity by persisting in the extratumoral peritoneal cavity

ABSTRACT: BiTE-secreting T cells effectively target ovarian cancer and prolong antitumor immunity by persisting in the extratumoral peritoneal cavity

PROVIDER: PRJNA905365 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22407836_1.fastq.gz	Fastqsanger.gz
	SRR22407836_2.fastq.gz	Fastqsanger.gz
	SRR22407837_1.fastq.gz	Fastqsanger.gz
	SRR22407837_2.fastq.gz	Fastqsanger.gz
	SRR22407838_1.fastq.gz	Fastqsanger.gz

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BiTE-secreting T cells effectively target ovarian cancer and prolong antitumor immunity by persisting in the extratumoral peritoneal cavity

Project description:Cancer immunotherapies can produce complete therapeutic responses, however outcomes in ovarian cancer (OC) are modest and while adoptive transfer of engineered T cells (ACT) has been evaluated in OC, durable effects are rarely observed. T cells lacking tumor specificity (bystander T cells) readily accumulate in tumors and leveraging bystander T cell activity represents a promising opportunity to enhance antitumor immunity following ACT. To this end, we have generated T cells that stably secrete a FRα-directed bispecific T cell engager (FR-B T cells), which robustly targeted FRα+ tumor cells in OC patient specimens and effectively engaged patient T cells present in the tumor microenvironment (TME). Therapeutic testing of FR-B T cells using an immunocompetent OC model demonstrated robust activity, with response duration dependent on both endogenous T cells and FR-B T cell persistence. Cytokine preconditioning prior to infusion produced less differentiated FR-B T cells and improved therapeutic efficacy, with mechanistic studies revealing preferential accumulation of TCF-1+ CD69-CD39- stem-like CD8+ FR-B T cells in the peritoneal cavity over solid tumors. These findings highlight the potential of FR-B T cell therapy in OC and suggest the peritoneal TME permits FR-B T cells to persist in the extratumoral space while actively directing antitumor immunity.

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