IND-Enabling Studies for a Clinical Trial to Genetically Program a Persistent Cancer-Targeted Immune System.

ABSTRACT:

Purpose

To improve persistence of adoptively transferred T-cell receptor (TCR)-engineered T cells and durable clinical responses, we designed a clinical trial to transplant genetically-modified hematopoietic stem cells (HSCs) together with adoptive cell transfer of T cells both engineered to express an NY-ESO-1 TCR. Here, we report the preclinical studies performed to enable an investigational new drug (IND) application.

Experimental design

HSCs transduced with a lentiviral vector expressing NY-ESO-1 TCR and the PET reporter/suicide gene HSV1-sr39TK and T cells transduced with a retroviral vector expressing NY-ESO-1 TCR were coadministered to myelodepleted HLA-A2/K^b mice within a formal Good Laboratory Practice (GLP)-compliant study to demonstrate safety, persiste

SUBMITTER: Puig-Saus C 

PROVIDER: S-EPMC6359988 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature