31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The Case of Missing Incommensurate Smectic A Phases

Two binary mixtures of polar liquid crystal materials were previously reported to exhibit three incommensurate smectic A phases predicted for such materials on the basis of phenomenological theory. Results of our recent high-resolution X-ray scattering experiments show that no incommensurate phases exist in the two systems. Wide coexistence regions are found at first order transitions between various frustrated smectic phases of these mixtures. These regions were previously identified as the incommensurate smectic A phases. The phase diagrams of the two systems determined with high-resolution X-ray technique are shown to be in excellent agreement with Baroisa-Prost-Lubensky theory.</p

Alendronate functionalized PLGA based nanoparticles for the effective treatment of osteoporosis-Formulation to in-vitro release kinetic studies

Osteoporosis is a bone disease caused due to the reducing bone mineral density. Porous and more fragile bones increase the risk of fractures. Hip, spine, shoulder, and wrist bones are commonly affected by osteoporosis. Low bone density is a leading cause of osteoporosis. The most efficient prescribed drugs for the treatment of osteoporosis are bisphosphonates drugs. Alendronate was the first FDA approved bisphosphonate drug for the treatment of osteoporosis. Osteoclast cells are the primary targeting site for alendronate, responsible for bone resorption. A biopharmaceutical classification system class III bisphosphonate acts as a potent, efficient, and bone resorption inhibitor drug. In the present study, alendronate functionalized PLGA based nanoparticles were developed by a solvent diffusion method and optimized for different process variables. The formulated nanoparticles were characterized for surface morphology, particle size distribution, surface charge and drug-polymer compatibility. The scanning electron microscopy and transmission electron microscopy results showed nanoparticle size in the range below 200 nm. The average particle size and zeta potential of the formulated nanoparticles were found to be 175.3 nm and -13.98 mV, respectively. The highest encapsulation efficiency was 65.23%. The release profile was dissolution medium dependent and followed by the Higuchi model of release kinetics

Synthesis and in vitro drug release of primaquine phosphate loaded PLGA nanoparticles

Plasmodium falciparum is one of the most common resistant Plasmodium species responsible for high rates of morbidity and mortality in malaria patients. Clinical guidelines for the management of Plasmodium falciparum include the use of a dose of primaquine phosphate resulting intolerable side effects. Therefore, the aim of this work was to formulate primaquine phosphate-loaded PLGA nanoparticles by using a nanoprecipitation method in order to increase its bioavailability to minimize drug intake. This leads to reduced toxicity and better therapeutic efficacy of the drug. The synthesized nanoparticles were characterized by using dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (XRD). TEM analysis revealed the presence of smooth spherical-shaped nanoparticles. The drug DLS analysis confirmed the presence of negatively charged nanoparticles with particle size in the range of 100-400 nm. The drug release study was performed to analyses different kinetic models like zero-order model, first-order model, Higuchi model, Hixson-Crowell model, and Korsmeyer-Peppas model

Impact of Biotic and Abiotic Stress on Survival of Lac Insects Kerria lacca Kerr. on Pigeonpea (Cajanus cajan (L.) Millsp)

Cajanus cajan is generally grown in rainfed condition. The crop is also a good annual host plant of lac insect. C. cajan is widely reported to have biotic stress due to insect pests on it. Lac insect is phloem sap feeder and hence imparts biotic stress. The present field study was conducted to evaluate the percent survival of lac insects&nbsp;on C. cajan by adjusting different levels of biotic and abiotic stress on the host plant. The biotic stress due to insect pests on C. cajan was minimised with periodic spray of contact insecticides. The varying level of biotic stress i.e., No, Low, Medium, and High level was maintained on C. cajan plants with lac insects on it. The three levels of abiotic stress in this experiment were considered in terms of soil moisture stress. It was managed through irrigation per plant through drip system, it was considered that creating different levels of moisture stress in soil will impact the host plant. The abiotic stress was of three levels i.e., Low, Medium, and High. The result reveals that survival percent of Lac insect from brood lac inoculation to the harvest of lac crop was highest 37.52 percent on C. cajan with one primary branch and its secondary branches with lac insect (L1- Low biotic stress). It was 32.13 percent (W3- Low soil moisture stress). The study indicates that biotic and abiotic stress play a major role in the survival of K. lacca