The challenge of applying genetically engineered T lymphocyte therapy to the treatment of solid organ tumors

A cross-sectional look at the clinical trial landscape (2003-2022)

Abstract

Genetically engineered T-lymphocyte therapy is based on the induction of the expression of chimeric CAR or TCR receptors on the membrane of T-lymphocytes extracted from the patient's body. These receptors are designed for specific recognition of tumor antigens. While in the field of hematology, the FDA approved 2017 the first therapy with T-CAR lymphocytes; in the case of solid organ tumors, numerous drugs have been tested in clinical trials without conclusive results. We have therefore conducted a review of the landscape of clinical trials with T-CAR/T-TCR for the treatment of solid organ tumors to analyze where this therapy is currently in its development, its limits, and challenges, and whether there are theoretical or preclinical foundations aimed at overcoming them. We found 297 trials published since 2003 in NIH's ClinicalTrials.gov, developed in 15 countries, mostly China (51.9%) and the USA (39.4%). The CAR receptor was used in 84.8% and TCR in 15.2%. Only 2.7% were in phase 2 or 2/3, only 14.5% were reported as completed or finished, and only 3.4% had published results. These data support the conclusion that preclinical phase strengthening is necessary before achieving a successful approach using T-CAR/T-TCR therapy for treating solid organ tumors.