Study of Anti-5T4 CAR-raNK Cell Therapy in Locally Advanced or Metastatic Solid Tumors

Summary

This study is a multicenter, open-label, investigator-initiated trial (IIT), divided into dose escalation (Part A) and dose extension (Part B) phases to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacokinetics (PD) and initial efficacy of conjugated antibody redirecting ready-to-use allogeneic NK (CAR-raNK) cells that target trophoblast glycoprotein (5T4) in patients with locally advanced or metastatic solid tumors.

Timeline

Start

2021-11-24

Primary completion

2023-04

Completion

2023-05

Publications

• Background Gras Navarro A, Bjorklund AT, Chekenya M. Therapeutic potential and challenges of natural killer cells in treatment of solid tumors. Front Immunol. 2015 Apr 29;6:202. doi: 10.3389/fimmu.2015.00202. eCollection 2015.
• Background Franks SE, Wolfson B, Hodge JW. Natural Born Killers: NK Cells in Cancer Therapy. Cancers (Basel). 2020 Jul 31;12(8):2131. doi: 10.3390/cancers12082131.
• Background Griffiths RW, Gilham DE, Dangoor A, Ramani V, Clarke NW, Stern PL, Hawkins RE. Expression of the 5T4 oncofoetal antigen in renal cell carcinoma: a potential target for T-cell-based immunotherapy. Br J Cancer. 2005 Sep 19;93(6):670-7. doi: 10.1038/sj.bjc.6602776.
• Background Shaw DM, Embleton MJ, Westwater C, Ryan MG, Myers KA, Kingsman SM, Carroll MW, Stern PL. Isolation of a high affinity scFv from a monoclonal antibody recognising the oncofoetal antigen 5T4. Biochim Biophys Acta. 2000 Dec 15;1524(2-3):238-46. doi: 10.1016/s0304-4165(00)00165-3.
• Background Redchenko I, Harrop R, Ryan MG, Hawkins RE, Carroll MW. Identification of a major histocompatibility complex class I-restricted T-cell epitope in the tumour-associated antigen, 5T4. Immunology. 2006 May;118(1):50-7. doi: 10.1111/j.1365-2567.2006.02338.x.
• Background Stern PL, Harrop R. 5T4 oncofoetal antigen: an attractive target for immune intervention in cancer. Cancer Immunol Immunother. 2017 Apr;66(4):415-426. doi: 10.1007/s00262-016-1917-3. Epub 2016 Oct 18.
• Background Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020 Feb 6;382(6):545-553. doi: 10.1056/NEJMoa1910607.
• Background Xia H, Wang Y, Sun HL, Gao LY, Cao Y, Zaongo SD, Zeng RN, Wu H, Zhang MJ, Ma P. Safety and efficacy of allogeneic natural killer cell immunotherapy on human immunodeficiency virus type 1 immunological non-responders: a brief report. Chin Med J (Engl). 2020 Dec 5;133(23):2803-2807. doi: 10.1097/CM9.0000000000001189.
• Background Nagai K, Harada Y, Harada H, Yanagihara K, Yonemitsu Y, Miyazaki Y. Highly Activated Ex Vivo-expanded Natural Killer Cells in Patients With Solid Tumors in a Phase I/IIa Clinical Study. Anticancer Res. 2020 Oct;40(10):5687-5700. doi: 10.21873/anticanres.14583.

Drugs

Indications

No indication recorded.