Julia Maria Müller

Allorestricted T lymphocytes with a high avidity T‐cell receptor towards NY‐ESO‐1 have potent anti‐tumor activity

The cancer‐testis antigen NY‐ESO‐1 has been targeted as a tumor‐associated antigen by immunotherapeutical strategies, such as cancer vaccines. The prerequisite for a T‐cell‐based therapy is the induction of T cells capable of recognizing the NY‐ESO‐1‐expressing tumor cells. In this study, we generated human T lymphocytes directed against the immunodominant NY‐ESO‐1157–165 epitope known to be naturally presented with HLA‐A*0201. We succeeded to isolate autorestricted and allorestricted T lymphocytes with low, intermediate or high avidity TCRs against the NY‐ESO‐1 peptide. The avidity of the established CTL populations correlated with their capacity of lysing HLA‐A2‐positive, NY‐ESO‐1‐expressing tumor cell lines derived from different origins, e.g. melanoma and myeloma. The allorestricted NY‐ESO‐1‐specific T lymphocytes displayed TCRs with the highest avidity and best anti‐tumor recognition activity. TCRs derived from allorestricted, NY‐ESO‐1‐specific T cells may be useful reagents for redirecting primary T cells by TCR gene transfer and, therefore, may facilitate the development of adoptive transfer regimens based on TCR‐transduced T cells for the treatment of NY‐ESO‐1‐expressing hematological malignancies and solid tumors.

Molar Mass Control by Diethyl Zinc in the Polymerization of Butadiene Initiated by the Ternary Catalyst System Neodymium Versatate/Diisobutylaluminum Hydride/Ethylaluminum Sesquichloride

The polymerization of 1,3‐butadiene (BD) catalyzed by the ternary Ziegler/Natta catalyst system neodymium versatate (NdV)/diisobutylaluminum hydride (DIBAH)/ethylaluminum sesquichloride (EASC) is investigated in regard to molar mass control by diethyl zinc (ZnEt2). Within the investigated range of ratios of ZnEt2 to NdV, the features of a living polymerization with a reversible exchange of the living polybutadienyl chains between neodymium and zinc are observed. In summary, ZnEt2 can be considered as an efficient molar mass control agent, which has a negligible impact on polymerization rates. In addition to the reduction of molar masses, ZnEt2 also reduces the polydispersity (PDI) and leads to a decrease of the cis‐1,4‐content.

Comparison of the Solvents n‐Hexane, tert‐Butyl Benzene and Toluene in the Polymerization of 1,3‐Butadiene with the Ziegler Catalyst System Neodymium Versatate/Diisobutylaluminum Hydride/Ethylaluminum Sesquichloride

The influence of the solvents n‐hexane, tert‐butyl benzene (TBB) and toluene on the Nd‐catalyzed polymerization of butadiene was studied. Special emphasis was placed on polymerization kinetics and on the evolution of molar masses and molar mass distributions with monomer conversion. Distinct differences were found between the three solvents. From the polymerization kinetics there is evidence which supports Porris view on the competitive coordination between aromatic solvents and butadiene to active Nd‐sites. In addition, there are indications for the irreversible transfer of benzyl‐H‐atoms from toluene to active allyl‐anionic polymer chains. The evolution of molar mass distributions with monomer conversion provides evidence for the existence of two active catalyst species which are present in all three solvents. One of these two species is highly reactive (“hot”) and short‐lived. This species generates BR with high molar mass. The second species has a low reactivity and lives throughout the entire course of the polymerization. In n‐hexane the “hot”, short‐lived species is present only at the start of the polymerization, whereas in TBB and toluene, the short‐lived species becomes evident at monomer conversion>10% and is constantly (re)generated. Cis‐1,4‐contents determined at final monomer conversion are not in line with other available studies in this field.