Improving cellular cancer vaccines

Immunization with cancer cells is of great demand in anti-cancer therapy. However, current cellular vaccines are inefficient and there are questions regarding their overall safety. We report a simple and straightforward approach for improving of cellular cancer vaccines. Through treatment of cancer cell cultures with purified protease, it is possible to make preparations of cell-surface antigens that are free of intracellular content and contain two orders-of-magnitude less protein than the whole lysate of an equivalent number of cancer cells. Despite this difference in total protein content, protease-generated preparations stimulate anti-cancer responses from immune cells better those stimulated with cancer cells themselves. The composition of collected cell-surface antigens, prior to vaccination, can be directly compared with antigenic profile of target cancer cells by the proteomic footprinting. Any contaminates (cell parasites, viruses, toxins, prions, etc.) are easily separated from antigens by means of ultrafiltration. Thus, current cellular vaccines may be improved by replacing whole cancer cells with their isolated cell-surface antigens. Vaccines prepared in this manner are potentially more qualified, purer, and safer

Trypsin digest of cancer cells surface stimulates anti-tumor immune response better than cancer cells themselves

Antigens expressed on the surface of cancer cells are accessible targets for both humoral and cell-mediated immune responses, and are therefore potential candidates for vaccine development. Treating surface of live human breast adenocarcinoma cells (MCF-7) with trypsin yields a digest that contains 0.7% of total cell protein. Despite this difference, the trypsin digest stimulates in cytotoxicity assays anti-tumor response which kills 10-40% more cancer cells than those stimulated with cells themselves. From these results, we concluded that trypsin digest obtained from live cancer cells contains the essential antigens to induce an immune-mediated anti-tumor effect, and therefore, is candidate for anti-tumor vaccine development

Cell Proteomic Footprint

The authentication of mammalian cell cultures and their subpopulations are of tremendous demand in biotechnology and cell therapy. However, current techniques are either not efficient or can be very complex and expensive. Here we report a simple and straightforward approach for authentication of biological cells and their subpopulations with high speed, high throughput, low sample cost, and high sensitivity. We discovered that cell cultures treated with protease at soft, “non-killing” conditions release fragments of cell surface proteins, which composition is a strong characteristic of the cells. Mass spectrometric analysis of the released fragments allows a direct comparison of the produced mass spectrum with the mass spectrum of known cells. As an example, we applied this technique to verify subpopulations of human fibroblasts which have different origins and exhibit different medical characteristics

Scaling Properties of the Probability Distribution of Lattice Gribov Copies

We study the problem of the Landau gauge fixing in the case of the SU(2) lattice gauge theory. We show that the probability to find a lattice Gribov copy increases considerably when the physical size of the lattice exceeds some critical value $\approx2.75/\sqrt{\sigma}$, almost independent of the lattice spacing. The impact of the choice of the copy on Green functions is presented. We confirm that the ghost propagator depends on the choice of the copy, this dependence decreasing for increasing volumes above the critical one. The gluon propagator as well as the gluonic three-point functions are insensitive to choice of the copy (within present statistical errors). Finally we show that gauge copies which have the same value of the minimisation functional ($\int d^4x (A^a_\mu)^2$) are equivalent, up to a global gauge transformation, and yield the same Green functions.Comment: replaced with revised version; 23 pages, 7 figures, 27 table

Dynamic message-passing equations for models with unidirectional dynamics

Understanding and quantifying the dynamics of disordered out-of-equilibrium models is an important problem in many branches of science. Using the dynamic cavity method on time trajectories, we construct a general procedure for deriving the dynamic message-passing equations for a large class of models with unidirectional dynamics, which includes the zero-temperature random field Ising model, the susceptible-infected-recovered model, and rumor spreading models. We show that unidirectionality of the dynamics is the key ingredient that makes the problem solvable. These equations are applicable to single instances of the corresponding problems with arbitrary initial conditions, and are asymptotically exact for problems defined on locally tree-like graphs. When applied to real-world networks, they generically provide a good analytic approximation of the real dynamics.Comment: Final versio