Phase I Trial of Anti-PSMA Designer CAR-T Cells in Prostate Cancer: Possible Role for Interacting Interleukin 2-T Cell Pharmacodynamics as a Determinant of Clinical Response

Autor: Anthony Bais, Qiangzhong Ma, Stephen I. Cohen, A. Samer Al-Homsi, Erica M. Gomes, Howard Cabral, Mehrdad Abedi, Richard P. Junghans, Ritesh Rathore, Robin Davies, Agnes Lo
Rok vydání: 2016
Předmět:
Zdroj: The Prostate. 76:1257-1270
ISSN: 0270-4137
DOI: 10.1002/pros.23214
Popis: BACKGROUND Chimeric antigen receptor (CAR)-modified “designer” T cells (dTc, CAR-T) against PSMA selectively target antigen-expressing cells in vitro and eliminate tumors in vivo. Interleukin 2 (IL2), widely used in adoptive therapies, was proven essential in animal models for dTc to eradicate established solid tumors. METHODS Patients under­went chemotherapy condi­tion­ing, followed by dTc dosing under a Phase I escalation with continuous infusion low dose IL2 (LDI). A target of dTc escalation was to achieve ≥20% engraftment of infused activated T cells. RESULTS Six patients enrolled with doses prepared of whom five were treated. Patients received 109 or 1010 autologous T cells, achieving expansions of 20–560-fold over 2 weeks and engraftments of 5–56%. Pharmacokinetic and pharmacodynamic analyses established the impact of conditioning to promote expansion and engraftment of the infused T cells. Unexpectedly, administered IL2 was depleted up to 20-fold with high engraftments of activated T cells (aTc) in an inverse correlation (P
Databáze: OpenAIRE
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