The present invention provides improved Etanercept variants which comprise one (A105E), preferably two (A105E/L106F), amino acid substitutions regarding the Etanercept original amino acid sequence of SEQ ID NO: 3. These variants inhibit TNF activity but fail to neutralize human LT (hLT). Thus, they are proposed herein as a great alternative to be used in the clinic for the treatment of autoimmune or inflammatory diseases in which an exacerbated TNF activity is involved, since they prevent the side effects associated to the use of the original Etanercept molecule while retaining the TNF blocking activity.

The invention relates to a composition and related methods for reducing tumor volume and/or increasing the survival of a cancer patient. The composition comprises a recombinant MVA encoding a Tumor Associated Antigen (TAA) as well as 4-1BBL and/or CD40L and can be administered to a subject in any suitable manner, including by intravenous and/or intratumoral administration.

The described invention provides a tumor cell vaccine comprising genetically modified tumor cell line of a particular tumor type that stably expresses high levels of two or more immunomodulators. According to some embodiments, an immunogenic amount of the tumor cell line variants may be selected for concomitant expression of two or more of recombinant membrane expressed IgG1, CD40L, TNF-alpha, as well as membrane and soluble forms of GM-CSF, and Flt-3L peptides that are effective to elicit an anti-tumor immune response compared to the parent unmodified tumor cell line as measured in vitro by a one-way mixed lymphocyte tumor reaction assay using human peripheral blood mononuclear cells and the genetically modified allogeneic cell vaccine candidate. According to some embodiments, the tumor cell vaccine candidate will induce an immune response in the recipient cancer patient that cross reacts with the patient's own (autologous) tumor cells, the effects of which will be sufficient to result in enhanced anti-tumor immunity contributing to the increased survival of a vaccinated patient cohort compared to a matched unvaccinated patient cohort.