Antigen-independent and antigen-dependent methods to numerically expand CD19-specific CD8+ T cells

Area of Science:

• Immunotherapy
• Cellular Therapy
• Oncology

Background:

• Chimeric antigen receptor (CAR) T cells are a promising therapy for B-lineage leukemias and lymphomas.
• Current methods for expanding CAR T cells, like the rapid expansion protocol (REP), have limitations.
• The CD19-specific CAR, CD19R, is being investigated for its therapeutic potential.

Purpose of the Study:

• To compare the efficacy of an antigen expansion protocol (AEP) with the REP for expanding CD19R+CD8+ T cells.
• To evaluate the long-term propagation, CAR expression, and cytolytic activity of T cells expanded by AEP versus REP.
• To determine if AEP can generate clinically relevant numbers of CAR T cells with enhanced functionality.

Main Methods:

• CD19R+CD8+ T cells were expanded using either REP or AEP.
• AEP involved K562-derived artificial antigen-presenting cells coexpressing CD19, 4-1BB ligand, and MHC-related chains A.
• Expansion was conducted over 28 days with recombinant human interleukin-2 and interleukin-15.

Main Results:

• The AEP successfully achieved numerical expansion of CD19R+CD8+ T cells to meet clinical demands.
• AEP demonstrated superiority over REP, resulting in T cells with higher CD19R CAR expression.
• T cells expanded via AEP exhibited improved redirected cytolytic activity.

Conclusions:

• The antigen expansion protocol (AEP) provides robust propagation of CD19R+CD8+ T cells.
• AEP is a viable alternative to REP for CAR T cell manufacturing in clinical trials.
• This method supports the use of AEP under current good manufacturing practices for CAR+ T cells.