TY  - JOUR
AU  - Arndt, Claudia
AU  - Tunger, Antje
AU  - Wehner, Rebekka
AU  - Rothe, Rebecca
AU  - Kourtellari, Eleni
AU  - Luttosch, Stephanie
AU  - Hannemann, Katharina
AU  - Koristka, Stefanie
AU  - Loureiro, Liliana R
AU  - Feldmann, Anja
AU  - Tonn, Torsten
AU  - Link, Theresa
AU  - Kuhlmann, Jan Dominik
AU  - Wimberger, Pauline
AU  - Bachmann, Michael Philipp
AU  - Schmitz, Marc
TI  - Palbociclib impairs the proliferative capacity of activated T cells while retaining their cytotoxic efficacy.
JO  - Frontiers in pharmacology
VL  - 14
SN  - 1663-9812
CY  - Lausanne
PB  - Frontiers Media
M1  - DKFZ-2023-00395
SP  - 970457
PY  - 2023
AB  - The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib is an emerging cancer therapeutic that just recently gained Food and Drug Administration approval for treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor (Her)2-negative breast cancer in combination with the ER degrader fulvestrant. However, CDK4/6 inhibitors are not cancer-specific and may affect also other proliferating cells. Given the importance of T cells in antitumor defense, we studied the influence of palbociclib/fulvestrant on human CD3+ T cells and novel emerging T cell-based cancer immunotherapies. Palbociclib considerably inhibited the proliferation of activated T cells by mediating G0/G1 cell cycle arrest. However, after stopping the drug supply this suppression was fully reversible. In light of combination approaches, we further investigated the effect of palbociclib/fulvestrant on T cell-based immunotherapies by using a CD3-PSCA bispecific antibody or universal chimeric antigen receptor (UniCAR) T cells. Thereby, we observed that palbociclib clearly impaired T cell expansion. This effect resulted in a lower total concentration of interferon-γ and tumor necrosis factor, while palbociclib did not inhibit the average cytokine release per cell. In addition, the cytotoxic potential of the redirected T cells was unaffected by palbociclib and fulvestrant. Overall, these novel findings may have implications for the design of treatment modalities combining CDK4/6 inhibition and T cell-based cancer immunotherapeutic strategies.
KW  - CAR T cell (Other)
KW  - CDK4/6 (Other)
KW  - adoptive T cell therapy (Other)
KW  - bispecific antibody (Other)
KW  - cancer immunotherapy (Other)
KW  - fulvestrant (Other)
KW  - palbociclib (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36817127
C2  - pmc:PMC9935825
DO  - DOI:10.3389/fphar.2023.970457
UR  - https://inrepo02.dkfz.de/record/271263
ER  -