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| Home > Publications database > Palbociclib impairs the proliferative capacity of activated T cells while retaining their cytotoxic efficacy. |
| Home > Publications database > Palbociclib impairs the proliferative capacity of activated T cells while retaining their cytotoxic efficacy. |
| Journal Article | DKFZ-2023-00395 |
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2023
Frontiers Media
Lausanne
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Please use a persistent id in citations: doi:10.3389/fphar.2023.970457
Abstract: 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.
Keyword(s): CAR T cell ; CDK4/6 ; adoptive T cell therapy ; bispecific antibody ; cancer immunotherapy ; fulvestrant ; palbociclib
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