Applications of tumor neoantigens to precision immunotherapy / 中华微生物学和免疫学杂志

Tumor neoantigens generated from somatic mutations can be presented by major histo-compability complex (MHC) molecules and elicit specific immune response against cancer. Therapeutic vac-cines and specific T cells targeting tumor neoantigens will realize the potential of precision immunotherapy in cancer treatment. Along with the development of methods for predicting neoantigens, individualized cancer immunotherapy strategies will be widely adopted. In the present review, we discuss the current state of the prediction approaches and clinical applications of neoantigens, as well as the challenges that remain to be ad-dressed in order to improve immunotherapy targeting neoantigens.

Melanoma antigen-A family in tumor / 国际肿瘤学杂志

As a tumor-specific antigen highly expressed in various types of tumors, MACE-A does not exist in normal adult tissues, except for testis and placenta. Therefore MAGE-A antigens are regarded. tumor specific antigen,and have significant significance for cancer immunotherapy.

Preparation and antitumor immunity of long circulating Nano-Liposome encapsulated tumor specific antigen / 细胞与分子免疫学杂志

AIM: To prepare Nano-Liposome encapsulated MAGE3/HSP70(NL M3H) and study its character and antitumor immunity in mouse. METHODS: NL M3H was prepared by the thin film-dispersion ultrasonic. The shape and size of NL M3H were detected by electron microscope. The encapsulation rate, drug-carrying capacity, stability and the releasing character were tested by Sephedex-G100 gel filtration. The mouse was immunized by NL M3H, and the antitumor immunity was detected by ELISPOT and LDH release assay. RESULTS: The mean size of NL M3H was lower than 100 nm. The encapsulation rate was 38％.The drug content was 0.038 g/L. NL M3H has good stability after stored in 4℃ for 6 months. The releasing profile showed that 74 percent of proteins was released during the first 24 hours in saline. The results of ELISPOT and LDH release assay showed that NL M3H generated tumor specific cytotoxic T lymphocyte(CTL)to damage tumor cel1. CONCLUSION: NL M3H has novel characters, it can generate specific CTL to kill tumor cell, and can be used as new kind of vaccine agsinst tumor.

Expression of MAGE 3 Gene Products in Uterine Cervical Carcinoma / 대한산부인과학회잡지

OBJECTIVE: The human MAGE 3 gene encodes tumor specific antigens that are recognized by autologue cytotoxic T lymphocytes (CTL). The MAGE 3 gene is expressed not only in melanoma but in the other malignant tumors as well. There is, however, little information on the expression of the gene in uterine cervical carcinomas. The author thus studied the expression of the MAGE 3 gene products in uterine cervical carcinoma and discuss the possibility of specific immunologic diagnosis using MAGE 3 gene products. METHODS: The expression of MAGE 3 gene product in 17 normal tissues of the cervix, 32 cervical intraepithelial neoplasia (8 CIN I, 10 CIN II, 14 CIS), and 43 invasive cervical carcinomas was studied by immunohistochemistry using anti-MAGE 3 mAb 57B in paraffin sections RESULTS: No expression of MAGE 3 gene product was detected in normal cervical tissues and in cervical intraepithelial neoplasias. The expression of MAGE 3 gene product was detected in 30.2% (13/43) of invasive cervical carcinomas. The MAGE 3 gene product was stained as a cytoplasmic protein in cancer cells. No statistically significant differences were observed between MAGE 3 gene product expression status and clinicopathologic parameters. CONCLUSIONS: The MAGE 3 gene products was expressed in invasive cervical carcinoma tissues.

Tumor-associated proteins in rat submandibular gland induced by DMBA and irradiation / 대한구강악안면방사선학회지

This study was performed in order to identify changes of the plasma membrane proteins in rat submandibular gland tumors induced by 7,12-dimethylbenz[a]anthracene [DMBA] and X-irradiation. Two kinds of tumor associated membrane proteins (protein A and B) were isolated with 3 M KCl extraction from rat submandibular gland tumors induced by DMBA and X-irradiation. To identify their antigenicities, immunoelectrophoresis and double immunodiffusion was carried out with various proteins extracted from liver, heart, skin and pancreas of adult rats and from embryonic liver, heart and skin. The rabbit antisera against the protein A did not cross-react with any of the proteins extracted from the above mentioned tissues, suggesting that protein A might be tumor specific antigen. However, the rabbit antisera against protein B was precipitated with proteins extracted from the liver of adult and embryonic rats. Polyacrylamide gel electrophoresis of these two proteins (A and B) showed that protein A was a dimer with molecular weights of 69,000 and 35,000 dalton, whereas protein B was a monomer with molecular weight of 50,000 dalton.

Characterization of Tumor Specific Antigens on the Plasma Membrane Surface of Rat Hepatomas lnduced by 3'-Me DAB and ldentification of the Common Tumor Specific Antigens from Rat Hepatomas lnduced by Different Chemical Hepatocarcinogens

Three different chemical carcinogens, 2-acetylaminofluorene (AAF), diethylnitrosamine(DENA), and 3'-methyl-4dimethylaminoazobenzene (3'-Me DAB) were used to induce hepatomas in rats. Plasma membrane surface proteins of normal rat liver cells and rat hepatomas were extracted with 3M KCI. From the analysis of the proteins of normal rat liver and rat hepatoma induced by 3'-Me DAB by discontinuous polyacrylamide gel electrophoresis(Disc-PAGE), under nonreducing and nondenaturing conditions polyacrylamide gel electrophoresis in the presence of SDS and 2-mercaptoethanol (SDS-PAGE), Sephadex G-200 gel permeation chromatography, DEAE-A50 ion-exchange chromatography and two-dimensional gel electrophoresis, at least three tumor specific antigens were identified. One had a molecular weigh of 66,000 (pl=6.79) while the other two had the same molecular weight 73,000 but differed in their isoelectric points (7.58 and 7.81). For immunological analysis of tumor specific antigens, the absorbed antiserum was prepared. Plasma membrane surface proteins of rat hepatoma induced by 3'-Me DAB were used to obtain New Zealand White male rabbit antiserum. Rabbit antiserum was then reacted with the proteins isolated from the plasma membrane surface of normal rat liver and the absorbed antiserum reacting specifically with the tumor specific antigens derived by 3'-Me DAB was obtained. Using the absorbed antiserum, the immunoreactivities of plasma membrane surface proteins isolated from rat hepatomas induced by 3'-Me DAB, AAF, and DENA were compared by Ouchterlony double immunodiffusion analysis and immunoelectrophoresis. To characterize the proteins reacting to the absorbed antiserum, immunoglobulin G was separated from the absorbed antiserum and coupled to cyanogen bromide-activated Sepharose CL-4B. The isolated proteins from the plasma membrane surface proteins of 3'-Me DAB-induced hepatoma using this immunoaffinity chromatography had molecular weights of 66,000 and 73,000. The localization of these proteins on surface plasma membranes of rat hepatomas induced by 3'-Me DAB was confirmed by an immunofluorescence technique. The experimental results revealed the existence of cross-reacting common antigens on the plasma membrane surface of rat hepatomas induced by different hepatocarcinogens.