%0 Journal Article
%A Arndt, Claudia
%A Tunger, Antje
%A Wehner, Rebekka
%A Rothe, Rebecca
%A Kourtellari, Eleni
%A Luttosch, Stephanie
%A Hannemann, Katharina
%A Koristka, Stefanie
%A Loureiro, Liliana R
%A Feldmann, Anja
%A Tonn, Torsten
%A Link, Theresa
%A Kuhlmann, Jan Dominik
%A Wimberger, Pauline
%A Bachmann, Michael Philipp
%A Schmitz, Marc
%T Palbociclib impairs the proliferative capacity of activated T cells while retaining their cytotoxic efficacy.
%J Frontiers in pharmacology
%V 14
%@ 1663-9812
%C Lausanne
%I Frontiers Media
%M DKFZ-2023-00395
%P 970457
%D 2023
%X 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.
%K CAR T cell (Other)
%K CDK4/6 (Other)
%K adoptive T cell therapy (Other)
%K bispecific antibody (Other)
%K cancer immunotherapy (Other)
%K fulvestrant (Other)
%K palbociclib (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36817127
%2 pmc:PMC9935825
%R 10.3389/fphar.2023.970457
%U https://inrepo02.dkfz.de/record/271263