Effect of Frequently Used Chemotherapeutic Drugs on Cytotoxic Activity of Human Cytotoxic T-lymphocytes (original) (raw)

2008, Journal of Immunotherapy

Tumors are considered to be possible targets of immunotherapy using stimulated and expanded cytotoxic Tlymphocytes (CTL). It is important to consider the drug-induced effects when chemotherapeutic regimens and CTL-mediated immunotherapy is planned to be used in parallel. In this study, we characterized the effect of 29 frequently used chemotherapeutic agents on the cytotoxic activity of autologous and allogeneic CTLs. We found that treatment of CTLs with the following drugs: docetaxel, vincristine, chlorambucil, mitomycin C, oxaliplatin, doxorubicin, and bleomycin effectively inhibited CTL-mediated killing, without affecting their viability. On the other hand, the following drugs enhanced or permitted efficient CTL-mediated killing in vitro at concentrations comparable with the maximally achieved therapeutic concentration in vivo in humans: daunorubicin, prednisolone, vinorelbine, cisplatin, methotrexate, hydroxyurea, cytarabine, cyclophosphamide, topotecan, epirubicin, fluorouracil, carboplatin, asparaginase, 6-mercaptopurine, and bortezomib. Our results could poten-tially be used in the future to design new CTL-based adjuvant immunotherapy protocols. Financial Disclosure: The authors have declared there are no financial conflicts of interest related to this work. Henriette Skribek and Michael Uhlin contributed equally to this work. Authors' contributions: The project was conceived and designed by Laszlo Szekely and Gyorgy Stuber. The experiments were mainly carried out and/or coordinated by Laszlo Markasz. Michael Uhlin created and cultures all CTL lines and LCLs used in the experiments. Gyorgy Stuber, Laszlo Markasz, and Rita Otvos took part in preparation of the microtiter plates for in vitro drug sensitivity assays. Laszlo Markasz and Rita Otvos were responsible for measuring the plates using the automated laser confocal fluorescent microscope. Laszlo Szekely and Emilie Flaberg wrote the computer programs QuantCapture 4.0 and CytotoxCount 3.0. Laszlo Markasz and Henriette Skribek analyzed and interpreted the data. Staffan Eksborg made comparable the in vitro results with the in vivo data. Eva Olah, Henriette Skribek together with the other authors have been involved in the planning of the experimental details, and the drafting, and critical reading of the manuscript. All authors read and approved the final manuscript. Reprints: Laszlo Szekely,