Antibody-dependent cellular cytotoxicity (ADCC) is one means by which macrophages (as well as natural killer cells and granulocytes) elicit a cytotoxic response. This is achieved via interaction of the Fc--receptor (CD64) with the Fc portion of antibody bound to target cells. We have created a chimeric CD64 molecule that incorporates a single chain Fv molecule, targeted against human carcinoembryonic antigen (CEA), fused to the membrane spanning and cytosolic domains of human CD64. Following adenoviral transfer to primary human monocytes, this chimeric CD64 receptor induced antigen-specific cytokine secretion during culture on immobilised CEA protein or on CEA-expressing tumour cells. Moreover, CEA targeted, but not control, monocytes effectively retarded CEA-positive tumour cell growth in vitro. Importantly, targeted monocyte cultures significantly reduced in vivo tumour growth rates in xenograft studies resulting in improved survival rates over that of control monocyte cultures. These data suggest that genetically directing monocytes against tumour antigens may be a useful means of achieving an immunotherapeutic response.

Given the failure of conventional treatments for glioblastoma, gene therapy has gained interest considerable in recent years. Gliomas are associated with a state of immunosuppression, which appears to be partially mediated by an increase in secretion of transforming growth factor-β (TGF-β) from glioma cells. Decorin, a small proteoglycan which can bind to and inactivate TGF-β, has been successfully used as an antitumor strategy on stably transfected tumor cells and has been shown to cause growth suppression in neoplastic cells of various histological origins. In this paper, we investigated the use of gene therapy to deliver the decorin transgene in a site-specific manner in an experimental model of intracranial gliomas. Our aim was to inhibit the glioma-associated immunosuppressive state, and prolong the survival of tumor-bearing rats. We studied the effects of decorin gene transfer in the rat CNS-1 glioma model. To assess the effect of ectopic expression of decorin on glioma progression in vivo, stably transfected CNS-1 cells expressing decorin were implanted into the brain parenchyma of syngeneic Lewis rats. The rats implanted with CNS-1 cells expressing decorin survived significantly longer than those in the control groups which received CNS-1 cells that did not express decorin (P<.0001). We then investigated whether the survival observed with decorin expressing cells could be mimicked in vivo, using recombinant adenoviruses (RAds) expressing the decorin gene under the control of two different promoters: the human immediate-early cytomegalovirus (h-IE-CMV) and the glial fibrillary acidic protein (GFAP). In vivo results showed that administration of RAd expressing the human decorin under the control of h-IE-CMV promoter has a small, but significant effect in prolonging the survival of experimental tumor bearing rats (P<.0001). Our data indicate that ectopic decorin expression has the potential to slow glioma progression in vivo. Our results also indicate that expression of decorin has to be present in all cells which constitute the intracranial tumor mass for the inhibition of tumor growth and prolongation of the life expectancy of tumor-bearing rats to be effective.

The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals who were previously primed with BBIBP-CorV vaccines were divided into three arms on their choice as heterologous regimens BBIBP-CorV/PastoCovac (n = 68), BBIBP-CorV/PastoCovac Plus (n = 72) and homologous BBIBP-CorV (n = 74). PastoCovac booster recipients achieved the highest rate of anti-Spike IgG titer rise with a fourfold rise in 50% of the group. Anti-RBD IgG and neutralizing antibody mean rise and fold rise were almost similar between the PastoCovac and PastoCovac Plus booster receivers. The antibody durability results indicated that the generated antibodies were persistent until day 180 in all three groups. Nevertheless, a higher rate of antibody titer was seen in the heterologous regimen compared to BBIP-CorV group. Furthermore, no serious adverse event was recorded. The protein subunit-based booster led to a stronger humoral immune response in comparison with the BBIP-CorV booster receivers. Both the protein subunit boosters neutralized SARS-CoV-2 significantly more than BBIP-CorV. Notably, PastoCovac protein subunit-based vaccine could be successfully applied as a booster with convenient immunogenicity and safety profile.