Specific Inhibition of Tumor Growth by T Cell Receptor-Drug Conjugates Targeting Intracellular Cancer-Testis Antigen NY-ESO-1/LAGE-1.

Despite the significant therapeutic advances in T-cell immunotherapy, many malignancies remain unresponsive, which might be because of the negative regulation of T cells by the tumor microenvironment (TME). T cells discriminate tumor cells and normal cells through T-cell receptors (TCRs); therefore, we generated a novel type of TCR-drug conjugates (TDCs) by referring antibody-drug conjugations (ADCs) to overcome the effects of the TME on T cells while preserving the specificity of TCR for tumor recognition. We selected HLA-A2/NY-ESO-1157-165 (peptide NY-ESO-1157-165 in complex with human leukocyte antigen serotype HLA-A*02:01) as the antigen and the antigen-specific TCR (1G4113) as the carrier. By sortase A-mediated ligation, we obtained three NY-TCR-vcMMAEs and further studied their properties, antitumor activity, and toxicity in vitro and in vivo. We found that all the NY-TCR-vcMMAEs had high endocytosis efficiency and specifically killed HLA-A2/NY-ESO-1157-165 positive tumor cells. In xenograft models, one of the TDCs, NY-TCR-2M, was effectively and specifically distributed into tumor tissues and inhibited tumor growth without inducing obvious toxicity. Our results demonstrated that TCRs can be carriers of toxic payloads and that the TDCs thus formed can specifically inhibit tumor growth, neglecting the immune microenvironment.

[Cost Analysis of Dog Deworming in Echinococcosis Control Program in Daofu，Sichuan Province].

Objective: To estimate the cost of dog deworming in Daofu, Sichuan Province and analyze the factors influencing the cost, in order to provide a scientific basis for the investment for echinococcosis control. Methods: Thirty villages were randomly selected in Daofu, Sichuan Province in November 2015, according to the proportion of agricultural and pastoral areas. Data concerning the cost during each step of dog deworming were collected. The unit cost was estimated, the cost composition in each step, element, and institution were described, and the main cost-influencing factors were analyzed using the linear regression method. Results: The mean cost of dog deworming in the 30 surveyed villages was 3.76 yuan/dog-times, comprising drug cost of 0.38 yuan/dog-times, bait cost of 0.37 yuan/dog-times, drug delivery cost of 0.09 yuan/dog-times, mobilization cost of 0.19 yuan/dog-times, household deworming cost of 2.05 yuan/dog-times, faeces disposal cost of 0.35 yuan/dog-times, training cost of 0.29 yuan/dog-times, and supervision cost of 0.04 yuan/dog-times. Among the deworming steps, household deworming cost occupied the most （2.05 yuan/dog-times）; among the cost elements, labour cost had the highest proportion （2.55 yuan/dog-times）; among the different-leveled institutions, village-level cost was the most important part（2.82 yuan/dog-times）. Linear regression analysis revealed that the type of production and the distance among households were the major influencing factors. The labour price was the most sensitive factor for cost-estimation in the dog deworming activities. Conclusion: The labor cost of dog deworming is very high. Governments should increase investment according to local situations.

Modeling the heat transfer problem for the novel combined cryosurgery and hyperthermia system.

A multidimensional, finite element analysis (FEA) for the freezing, holding, rewarming and heating processes of biological tissues during the cryosurgery process of the new Combined Cryosurgery/Hyperthermia System is presented to theoretically test its validity. The tissues are treated as nonideal materials freezing over a temperature range, and the thermophysical properties of which are temperature dependent. The enthalpy method is applied to solve the highly nonlinear problem. It was found that when the same boundary condition and the same target tissue presented, the novel Cryosurgery/Hyperthermia System could supply the target tissue an approximative cooling rate, a much lower minimal temperature, a much greater warming rate, and a much greater thermal gradients compared with that of the simplified Endocare system. The numerical simulation indicates that the novel combined cryosurgery and hyperthermia system can provide an excellent curative effect in the corresponding cryotherapy. And the most attractive feature of this FEA framework is that it can be easily mastered by the surgeon without in-depth theory of heat transfer to analyze the cryosurgery process beforehand due to the friendly GUI (graphical user interface) of Ansys software.