Publications by authors named "Meera Subramaniyam"
We recently described a low-affinity second-generation CD19 chimeric antigen receptor (CAR) CAT that showed enhanced expansion, cytotoxicity, and antitumor efficacy compared with the high-affinity (FMC63-based) CAR used in tisagenlecleucel, in preclinical models. Furthermore, CAT demonstrated an excellent toxicity profile, enhanced in vivo expansion, and long-term persistence in a phase 1 clinical study. To understand the molecular mechanisms behind these properties of CAT CAR T cells, we performed a systematic in vitro characterization of the transcriptomic (RNA sequencing) and protein (cytometry by time of flight) changes occurring in T cells expressing low-affinity vs high-affinity CD19 CARs following stimulation with CD19-expressing cells.
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- The study evaluated the safety and effectiveness of using allodepleted donor T cells (ADTs) to enhance immune recovery in patients following matched unrelated donor (MUD) stem cell transplants, particularly after treatment with alemtuzumab for hematological cancers.
- Results showed a trend toward higher CD3+ T-cell counts at 4 months for those receiving ADTs compared to the control group, but the difference was not statistically significant, and a few patients achieved normal T-cell levels.
- While ADTs were deemed safe, the method's limited effect on T-cell reconstitution suggests it might be more beneficial in cases that involve more aggressive T-cell depletion.