Trudy Straetemans, Guido J. J. Kierkels, Ruud Doorn, Koen Jansen, Sabine Heijhuurs, Joao M. dos Santos, Anna D. D. van Muyden, Henri Vie, Béatrice Clemenceau, Reinier Raymakers, Moniek de Witte, Zsolt Sebestyén, Jürgen Kuball
Abstract
γ9δ2T cells play a critical role in daily cancer immune surveillance by sensing cancer-mediated metabolic changes. However, a major limitation of the therapeutic application of γ9δ2T cells is their diversity and regulation through innate co-receptors. In order to overcome natural obstacles of γ9δ2T cells, we have developed the concept of T cells engineered to express a defined γδT cell receptor (TEGs). This next generation of chimeric antigen receptor engineered T (CAR-T) cells not only allows for targeting of hematological but also of solid tumors and, therefore, overcomes major limitations of many CAR-T and γδT cell strategies. Here, we report on the development of a robust manufacturing procedure of T cells engineered to express the high affinity Vγ9Vδ2T cell receptor (TCR) clone 5 (TEG001). We determined the best concentration of anti-CD3/CD28 activation and expansion beads, optimal virus titer, and cell density for retroviral transduction, and validated a Good Manufacturing Practice (GMP)-grade purification procedure by utilizing the CliniMACS system to deplete non- and poorly-engineered T cells. To the best of our knowledge, we have developed the very first GMP manufacturing procedure in which αβTCR depletion is used as a purification method, thereby delivering untouched clinical grade engineered immune cells. This enrichment method is applicable to any engineered T cell product with a reduced expression of endogenous αβTCRs. We report on release criteria and the stability of TEG001 drug substance and TEG001 drug product. The GMP-grade production procedure is now approved by Dutch authorities and allows TEG001 to be generated in cell numbers sufficient to treat patients within the approved clinical trial NTR6541. NTR6541 will investigate the safety and tolerability of TEG001 in patients with relapsed/refractory acute myeloid leukemia, high-risk myelodysplastic syndrome, and relapsed/refractory multiple myeloma.
Pharmacology, Toxicology and Pharmaceutical Science
6
5%
Other
7
6%
Unknown
54
44%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 December 2023.
All research outputs
#3,561,377
of 26,414,132 outputs
Outputs from Frontiers in immunology
#4,021
of 33,172 outputs
Outputs of similar age
#66,402
of 347,420 outputs
Outputs of similar age from Frontiers in immunology
#126
of 740 outputs
Altmetric has tracked 26,414,132 research outputs across all sources so far. Compared to these this one has done well and is in the 86th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 33,172 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.6. This one has done well, scoring higher than 87% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 347,420 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 740 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.
