Clinical Trial Update: CRISPR-Edited CD19 CAR T Therapy for Blood Cancers
The new candidate, known as PACE CART19, is developed at the University of Pennsylvania (UPenn) through CRISPR editing of healthy donor-derived T cells. PACE CART19 is developed for the treatment of CD19+ acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), Non-Hodgkin's lymphoma (NHL), and certain other CD19+ blood cancers that meet disease-specific criteria.
PACE CART19 cells
PACE CART19 cells are pre-manufactured as off-the-shelf allogeneic CAR-T cell doses.
Donor-derived T cells are transduced with a lentiviral vector to express a CD19-targeting chimeric antigen receptor (CAR), which targets the CD19 cell surface antigen that is expressed by all B-cell cancers and which has been an important therapeutic target for cancer immunotherapies.
The cells are further subjected to electroporation with CRISPR-Cas9 ribonucleoprotein complexes (RNP) to disrupt the genes that encode beta-2 microglobulin, Class II Major Histocompatibility Complex Transactivator (CIITA) and T cell receptor alpha chain (TRAC locus). These edits reduce or eliminate the expression of HLA class I and HLA class II molecules as well as remove the endogenous T cell receptor (TCR), to reduce the risk of self-presenting to recipient T cells and boost persistence in the new host after infusion.
The PACE CART19 trial
The Phase 1 trial, which is not yet recruiting, will assess the safety and feasibility of administering pre-manufactured PACE CART19 cells.
The trial is anticipated to enroll 36 adult participants who have documented CD19+ acute lymphoblastic leukaemia (ALL), chronic lymphocytic leukaemia (CLL), or Non-Hodgkin's lymphoma (NHL) with evidence of disease relapse or refractory disease that failed to respond adequately to certain previous therapies.
Individuals with certain other CD19+ blood cancers may also be considered if they can fulfill various disease-specific inclusion criteria regarding prior treatment and disease state.
The trial will comprise two experimental arms: Cohort A, which will include ALL patients, and Cohort B, which will include CLL and NHL patients. Patients in both cohorts will receive an intravenous (IV) infusion of PACE CART19 cells, and the study’s primary outcome measure will be to determine the recommended expansion dose cells in a 28-day time frame. The estimated study start date, i.e. the date on which the first patient will be enroled, is January 2022.
For more insights into how CRISPR is used to develop CAR-T cell therapies, you can check out our recent CAR T clinical roundup on this topic here.
We will continue to bring updates on the PACE CART19 as they emerge. In the meantime, you can view our CRISPR Medicine News Clinical Trials Database for a complete overview of gene-editing clinical trials.
EdiGene (GuangZhou) Inc.
University of Pennsylvania