Nanobody-liposomes as novel cancer vaccine platform to efficiently stimulate T cell immunity.

Cancer vaccines can be utilized in combination with checkpoint inhibitors to optimally stimulate the anti-tumor immune response. Uptake of vaccine antigen by antigen presenting cells (APCs) is a prerequisite for T cell priming, but often relies on non-specific mechanisms. Here, we have developed a novel vaccination strategy consisting of cancer antigen-containing liposomes conjugated with CD169- or DC-SIGN-specific nanobodies (single domain antibodies) to achieve specific uptake by APCs. Our studies demonstrate efficient nanobody liposome uptake by human and murine CD169+ and DC-SIGN+ APCs in vitro and in vivo when compared to control liposomes or liposomes with natural ligands for CD169 and DC-SIGN. Uptake of CD169 nanobody liposomes resulted in increased T cell activation by human APCs and stimulated naive T cell priming in mouse models. In conclusion, while nanobody liposomes have previously been utilized to direct drugs to tumors, here we show that nanobody liposomes can be applied as vaccination strategy that can be extended to other receptors on APCs in order to elicit a potent immune response against tumor antigens.

Effect of exercise versus relaxation on haemoglobin A1C in Black females with type 2 diabetes mellitus.

BACKGROUND: Evidence suggests that populations in Africa develop Type 2 diabetes mellitus (DM) at an increasing rate as they reject their traditional lifestyles. Diabetes is the tenth most common cause for total life years lost in females in South Africa. Physical activity is under-used in the management of type 2 DM in South Africa. AIM: To investigate the efficacy of an exercise intervention programme compared to relaxation exercises to decrease HbA1c over a period of 12 weeks, in type 2 DM female subjects. DESIGN: Single blind, double-intervention randomized trial. METHODS: Clinical measurements were done before and after the 12-week exercise and relaxation interventions. The interventions consisted of education and aerobic exercise for the exercise group, and education and relaxation for the second group. RESULTS: Adjusted baseline HbA1c change from baseline in the exercise group after 12 weeks was -0.39% (95%CI -0.80 to 0.02) and in the relaxation group -0.97% (95%CI -1.38 to 0.55) (p = 0.052). The results for the BMI were -0.07% kg/m2 (95%CI -0.2 to 0.14) in the exercise group versus -0.23 kg/m2 (95%CI -0.44 to 0.02) in the relaxation group (p = 0.28). The difference from baseline in distances covered following the 6 min walk test was statistically significantly greater (p < 0.01) in the exercise group: 46.76 m (95%CI 36.20-57.32) vs the relaxation group 22.7 m (95%CI 12.07-33.33). DISCUSSION: The exercise intervention failed to reduce the HbA1c to a greater extent than in the relaxation control group. Both groups improved significantly from baseline, probably due to the study effect.

Significance of low molecular weight C1q in systemic lupus erythematosus.

The significance of high serum concentrations of low molecular weight C1q (LMW-C1q) in patients with systemic lupus erythematosus (SLE) was studied. Concentrations of LMW-C1q were increased in SLE, but not in rheumatoid arthritis or acute poststreptococcal glomerulonephritis. Concentrations of LMW-C1q in SLE serum samples correlated with titres of anti-dsDNA and were inversely related to concentrations of normal C1q and C3. Serial studies in six patients, who had rising anti-dsDNA titres and who developed a major exacerbation requiring admission to hospital, showed that LMW-C1q increased in parallel with anti-dsDNA, reaching peak values of more than 2000% of normal just before or at the time of clinical relapse and decreasing during convalescence. Most marked increases in LMW-C1q were noted in the three patients in whom C1q concentrations remained normal, whereas increases were less in the three patients who had strongly depressed concentrations of normal C1q. A study of C1q biosynthesis by macrophages cultured from patients with SLE and high serum concentrations of LMW-C1q did not show impaired secretion of normal C1q in favour of LMW-C1q, but indicated that serum concentrations of LMW-C1q may reflect the synthetic rate of C1q in vivo. The results show that increased serum concentrations of LMW-C1q may be helpful in diagnosing SLE and suggest that serial determination of LMW-C1q in serum may have predictive value in monitoring patients with SLE.

Dissociation studies of DNA/anti-DNA complexes in relation to anti-DNA avidity.

Antibodies to dsDNA differ in their avidity towards the antigen. The electrostatic interaction between DNA and anti-DNA is sensitive to increases in pH and/or ionic strength and therefore, elution studies employing either of these permit discrimination between anti-dsDNA populations that differ in avidity. Another way to determine anti-dsDNA avidity is the calculation of Farr/PEG ratios. These are obtained by division of the amount of anti-DNA measured with the Farr assay (which does not detect low avidity anti-dsDNA) by the amount measured with the PEG assay (which does detect low avidity anti-dsDNA). With these separate approaches, we compared the sera of 17 SLE patients with nephritis with the sera of 17 patients with central nervous system (CNS) involvement. Farr/PEG ratios and sensitivity to high pH elution of anti-dsDNA in the sera of these patients both permitted discrimination between the two groups of patients. The anti-dsDNA of patients with nephritis was found to have a significantly higher avidity towards DNA than anti-dsDNA of patients with cerebral disease. We also observed a significant correlation between Farr/PEG ratios and the salt lability of anti-dsDNA.