Thermally Responsive Amphiphilic Conetworks and Gels Based on Poly(N‑isopropylacrylamide) and Polyisobutylene

Novel amphiphilic conetworks (APCN) consisting of thermoresponsive poly(N-isoproplyacrylamide) (PNiPAAm) cross-linked by hydrophobic methacrylate-telechelic polyisobutylene (MA-PIB-MA) were successfully synthesized in a broad composition range. The resulting PNiPAAm-l-PIB conetworks (“l” stands for “linked by”) were obtained by radical copolymerization of NiPAAm with MA-PIB-MA in tetrahydrofuran, a cosolvent for all the components. Low amounts of extractables substantiated efficient network formation. The composition dependent two glass transition temperatures (Tg) by DSC analysis indicate microphase separation of the cross-linked components without mixed phases. It was found that the PNiPAAm-l-PIB conetworks are uniformly swellable in both water and n-hexane; i.e., these new materials behave either as hydrogels or as hydrophobic gels in aqueous or nonpolar media, respectively. The uniform swelling in both polar and nonpolar solutes indicates cocontinuous (bicontinuous) phase morphology. The equilibrium swelling degrees (R) depend on composition, that is, the higher the PIB content, the lower the R in water and the higher in n-hexane. The PNiPAAm phase keeps its thermoresponsive behavior in the conetworks as shown by significant decrease of the swelling degree in water between 20 and 35 °C. The lower critical solubility temperature (LCST) values determined by DSC are found to decrease from 34.1 °C (for the pure PNiPAAm homopolymer) to the range of 25–28 °C in the conetworks, and the extent of the LCST decrease is proportional with the PIB content. Deswelling-swelling, i.e., heating–cooling, cycle indicates insignificant hysteresis in these new thermoresponsive materials. This indicates that PNiPAAm-l-PIB conetworks with predetermined and thermoresponsive swelling behavior can be designed and utilized in several advanced applications on the basis of results obtained in the course of this study

Influence of the Macromolecular architecture on the self-assembly of amphiphilic copolymers based on poly(<i>N</i>,<i>N</i>-dimethylamino-2-ethyl methacrylate) and poly(ε-caprolactone)

International audienc

First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity

Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient's surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients.Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin™), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine®), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide.Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naïve GBM patients (NCT01903330)

First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined all- and auto-immune tumor reactivity

Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggestan imminent death within 1–4.5 months. Supportive preclinical data, from a rat model, provided therational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologousantigens, derived from the patient’s surgically removed tumor tissue, which is administered together withallogeneic antigens from glioma tissue resected from other GBM patients. We now report the first resultsof the Gliovac treatment for treatment-resistant GBM patients.Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- andchemotherapy temozolomide, and for US patients, also bevacizumab (AvastinTM), were treated under acompassionate use/hospital exemption protocol. Gliovac was given intradermally, together with humanGM-CSF (Leukine®), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophos-phamide.Gliovac administration in patients that have failed standard of care therapies showed minimal toxicityand enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100%versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperatedpatients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our datasuggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiatedin recurrent, bevacizumab naïve GBM patients (NCT01903330)