Dataset Information

Simultaneous targeting of PD-1 and IL2RBY with radiation therapy to inhibit pancreatic cancer growth and metastasis

ABSTRACT: In patients with pancreatic ductal adenocarcinoma (PDAC), we show that response to radiation therapy (RT) is characterized by increased IL2R and IL2R expression, decreased ILR2 and exhaustion markers. The bispecific PD-1-targeted IL-2 variant (IL2v) immunocytokine with engineered IL-2 cis-targeted to PD-1 and abolished IL2R binding targets the activation of tumor-antigen specific T cells while rescuing them from Treg suppression. Using aPD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival along with profound increase in tumor-infiltrating polyfunctional CD8 T cell subsets with a transcriptionally and metabolically active phenotype, and preferential activation of antigen-specific CD8 T cells. In combination with single dose RT, aPD1-IL2v treatment results in a robust, durable expansion of polyfunctional CD8 T cells, T cell stemness, tumor-specific memory immune response, NK cell activation, and decreased Tregs. These data show that the novel aPD1-IL2v, leads to profound local and distant response in PDAC.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Anthony Saviola

LAB HEAD: Sana D. Karam

PROVIDER: PXD040266 | Pride | 2024-05-24

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	RT_CD8_1_S1-C1_1_549.d.zip	Other
	RT_CD8_2_S1-C2_1_551.d.zip	Other
	RT_CD8_3_S1-C3_1_552.d.zip	Other
	RT_G1M1_CD8_S1-C2_1_616.d.zip	Other
	RT_G1M1_NK_S1-C1_1_615.d.zip	Other

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Publications

Simultaneous targeting of PD-1 and IL-2Rβγ with radiation therapy inhibits pancreatic cancer growth and metastasis.

Piper Miles M Hoen Maureen M Darragh Laurel B LB Knitz Michael W MW Nguyen Diemmy D Gadwa Jacob J Durini Greta G Karakoc Idil I Grier Abby A Neupert Brooke B Van Court Benjamin B Abdelazeem Khalid N M KNM Yu Justin J Olimpo Nicholas A NA Corbo Sophia S Ross Richard Blake RB Pham Tiffany T TT Joshi Molishree M Kedl Ross M RM Saviola Anthony J AJ Amann Maria M Umaña Pablo P Codarri Deak Laura L Klein Christian C D'Alessandro Angelo A Karam Sana D SD

Cancer cell 20230427 5

In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL-2Rβ and IL-2Rγ along with decreased IL-2Rα expression. The bispecific PD1-IL2v is a PD-1-targeted IL-2 variant (IL-2v) immunocytokine with engineered IL-2 cis targeted to PD-1 and abolished IL-2Rα binding, which enhances tumor-antigen-specific T cell activation while reducing regulatory T cell (Treg) suppression. Using PD1-IL2v in orthotopic PDAC KPC-driven tumor ...[more]

PMID: 37116489

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