Abstract 568P
Background
Ovarian and endometrial cancers are commonly occurring cancers in women with very limited treatment options for relapse and metastasis. While immune checkpoint inhibitors have generated unprecedented responses in certain other cancer types, results from early attempts in ovarian and endometrial cancers have been suboptimal. To develop a CAR-T therapy against these cancers, multi-omics data mining identified ALPP (alkaline phosphatase, placental), a cell surface protein with expression restricted to female reproductive tissues, as a potential target.
Methods
To validate its tumor-specific expression, immunohistochemical arrays were performed to assess cell surface display of ALPP in normal and cancerous tissues. An anti-ALPP CAR (TC-A101) was developed and validated for its targeting specificity against multiple ALP homologs, as well as its killing efficacy in vitro. The pre-clinical efficacy of this CAR was validated in an animal model of ovarian cancer peritoneal metastasis. A phase I clinical trial of TC-A101 for recurring and metastatic ovarian and endometrial cancer treatment was initiated to evaluate the safety, maximum tolerated dose, and clinical efficacy of this anti-ALPP CAR-T.
Results
Preclinical models demonstrate that TC-A101 T cell administration significantly reduces tumor burdens and extends the survival of mice bearing metastatic SiHa tumors and ascites. Three patients have been treated with low dose of TC-A101 without cytokine release syndrome manifestation or any other CAR-T related adverse events. We observed objective tumor regression in two of these three patients, with one patient reaching the threshold of partial response.
Conclusions
The preclinical and initial clinical findings reported here indicate that TC-A101 T cell immunotherapy is safe and potentially efficacious against female reproductive cancers expressing ALPP.
Clinical trial identification
NCT04627740.
Editorial acknowledgement
Legal entity responsible for the study
Xinqiao Hospital, Third Military Medical University, China.
Funding
Guangdong TCRCure Biopharma Technology Co., Ltd.
Disclosure
Z.Su: Financial interest, Personal, Other, Member of Board of Directors: Guangdong TCRCure Biopharma Technology Co., Ltd. All other authors have declared no conflicts of interest.