Poster Presentation 35th Lorne Cancer Conference 2023

Glypican-1 CAR T-cells as a Novel Immunotherapy for Ovarian Cancer (#154)

Lizamarie SB Goonetilleke 1 , Noor A Lokman 1 , Zoe K Price 1 , Wanqi Wang 1 , Veronika Bandara 2 , Silvana Napoli 2 , Batjargal Gundsambuu 2 , Martin K Oehler 3 , Simon R Barry 2 , Carmela Ricciardelli 1
  1. Adelaide Medical School , University of Adelaide, Adelaide, South Australia, Australia
  2. Molecular Immunology, Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia
  3. Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, South Australia, Australia

Ovarian cancer is the 5th most diagnosed cancer with high-grade serous ovarian cancer (HGSOC) making up nearly 70% of ovarian cancer patients. There is a need to develop novel treatment strategies as most patients diagnosed with HGSOC respond to chemotherapy but eventually develop chemotherapy resistance. Glypican-1 (GPC1), a heparan sulphate proteoglycan, has been identified as a therapeutic target for multiple cancers, however, there is limited literature on its role in ovarian cancer. This study investigated whether GPC1 is associated with ovarian cancer progression and whether it could be used as a potential target for HGSOC. The expression of GPC1 in ovarian cancer cell lines and primary cells was characterized using qRT-PCR and western blots. The cytotoxic effects of GPC1 CAR-T cells were assessed on ovarian cancer cell lines and primary serous ovarian cancer cells using monolayer assays and 3D spheroid assays. Analysis of online databases confirmed that GPC1 mRNA expression is increased in ovarian cancer compared to fallopian tubes (p <0.001) and high GPC1 expression in HGSOC is associated with reduced progression free survival (p=0.0015) and overall survival (p=0.00026). High GPC1 protein levels were significantly increased following relapse compared to matching tissues at diagnosis and associated with reduced progression-free survival in a tissue microarray cohort of HGSOC (n=93, p=0.031).  GPC1 CAR-T cells were cytotoxic and significantly inhibited the survival of HGSOC and non-HGSOC ovarian cancer cell in monolayer and reduced 3D-spheroid area compared to untransduced CD3+ T cells.  GPC1 CAR-T cells were cytotoxic on primary ovarian cancers with high GPC1 expression. In conclusion, this study demonstrates that GPC1 CAR-T cells have great potential to be developed as a novel immunotherapy for ovarian cancer.