Abstract Book 2010 - CIMT Annual Meeting

047 Blaudszun | Cellular therapy
Adoptive transfer of ex vivo activated and antineoplastic drug
loaded T lymphocytes retargeted to EpCAM expressing tumours
André-René Blaudszun 1 , Anja Philippi 1 , Alice Borth 1 , Gerhard Moldenhauer 2 , Philipp Beckhove
2 , Hyeck-Hee Lee 1 and Ute Steinfeld 1
1 Cellular Immunotherapy Group, KIST Europe Forschungsgesellschaft mbH, Saarbrücken, Germany
2 Translational Immunology Unit, German Cancer Research Center, Heidelberg, Germany
T lymphocytes are often the first choice for adop-
tive cell therapy (ACT) against cancers, because
of their intrinsic cytolytic capacity. Unfortunately,
clinical trials have shown that the effectiveness of
ACT is limited. Among various therapeutic options,
chemotherapy remains the mainstay of treatment
for neoplasms. However, therapies based on antineoplastic
drugs are often accompanied by severe
adverse effects, because they are also harmful to
healthy constantly dividing cells and tissues.
Here, we describe a novel cancer therapy approach
that combines the specificity of retargeted T cells
with the high efficacy of chemotherapies. To enhance
the natural cytotoxic function of human lymphocytes,
ex vivo activated and expanded T cells were
loaded with a liposomal preparation of the secondgeneration
anthracycline idarubicin (LipoIda). Although
T lymphocyte viability was impaired upon
LipoIda treatment, mice experiments were carried
out to test the effectiveness of the living drug carriers
in vivo. When SKOV-3 xenograft mice were
treated with either unloaded or idarubicin-loaded
allogenic T cells in combination with the bispecific
antibody EpCAM×CD3, tumour growth was more
efficiently inhibited by the drug-containing cells.
To analyse the observed effect in more detail, we
compared the action of idarubicin-loaded T cells
with the effect of a co-administration of unloaded
T cells and free drug. Xenograft mice treated with
drug-containing T lymphocytes showed a stronger
inhibition of tumour growth than the control
animals suggesting that the combined T cell-drug
effect of LipoIda-treated T cells on malignant cell
proliferation is rather synergistic than additive.
Thus, redirection of antineoplastic drug-loaded
T lymphocytes represents a promising course of
action to treat human cancers. Since the administered
idarubicin amount lies below conventional
therapeutic doses, strong adverse effects typically
caused by chemotherapy are unlikely to occur in
our approach.
91