• Journal of Microbiology and Biotechnology
• /
• 제17권6호
• /
• pp.879-890
• /
• 2007

The identification of tumor antigens is essential for the development of anticancer therapeutic vaccines and clinical diagnosis of cancer. SEREX (serological analysis of recombinant cDNA expression libraries) has been used to identify such tumor antigens by screening sera of patients with cDNA expression libraries. SEREX-defined antigens provide markers for the diagnosis of cancers. Potential diagnostic values of these SEREX-defined antigens have been evaluated. SEREX is also a powerful method for the development of anticancer therapeutics. The development of anticancer vaccines requires that tumor antigens can elicit antigen-specific antibodies or T lymphocytes. More than 2,000 antigens have been discovered by SEFEX. Peptides derived from some of these antigens have been evaluated in clinical trials. This review provides information on the application of SEREX for identification of tumor-associated antigens (TAA) for the development of cancer diagnostics and anticancer therapeutics.

• Journal of Microbiology and Biotechnology
• /
• 제17권6호
• /
• pp.993-1001
• /
• 2007

The technique of serological analysis of antigens by recombinant cDNA expression library (SEREX) uses autologous patient sera as a screening probe to isolate tumor-associated antigens for various tumor types. Isolation of tumor-associated antigens that are specifically reactive with patient sera, but not with normal sera, is important to avoid false-positive and autoimmunogenic antigens for the cancer immunotherapy. Here, we describe a selection methodology to isolate patient sera-specific antigens from a yeast surface-expressed cDNA library constructed from 15 patient lung tissues with non-small cell lung cancer (NSCLC). Several rounds of positive selection using patient sera alone as a screening probe isolated clones exhibiting comparable reactivity with both patient and normal sera. However, the combination of negative selection with allogeneic normal sera to remove antigens reactive with normal sera and subsequent positive selection with patient sera efficiently enriched patient sera-specific antigens. Using the selection methodology described here, we isolated 3 known and 5 unknown proteins, which have not been isolated previously, but and potentially associated with NSCLC.

• 생명과학회지
• /
• 제17권6호통권86호
• /
• pp.841-846
• /
• 2007

종양항원의 동정과 발견은 암 백신 및 진단개발에 매우 중요하다. 암환자의 혈청에서 종양 항원를 동정하는 SEREX가 개발되어왔다. SEREX에서 동정된 종양항원은 진단의 분자 지표 뿐 만 아니라 항암 백신 개발에 응용되고 있다. 따라서 SEREX는 종양항원 동정에 사용되어지는 매우 강력한 방법이다. 항암 백신의 개발은 동정된 종양항원이 체 또는 T cell에 기초하여 작동하는지 해명하는 것이 중요한 요소이다. 이 논문은 강력한 종양항원의 동정 방법인 SEREX 의 응용에 관하여 고찰 할 것이다.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권7호
• /
• pp.4041-4047
• /
• 2013

Cancer vaccine development is in the process of becoming reality in future, due to successful phase II/III clinical trials. However, there are still problems due to the specificity of tumor antigens and weakness of tumor associated antigens in eliciting an effective immune response. Computational models to assess the vaccine efficacy have helped to improve and understand what is necessary for personalized treatment. Further research is needed to elucidate the mechanisms of activation of antigen specific cytotoxic T lymphocytes, decreased TREG number functionality and antigen cascade, so that overall improvement in vaccine efficacy and disease free survival can be attained. T cell epitomic based in sillico approaches might be very effective for the design and development of novel cancer vaccines.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제11권1호
• /
• pp.203-220
• /
• 1989

Ever since the expression of new tumor-specific antigens was reported during malignant transformation, studies on separation, purification and characterization of these proteins have been so activated recently. Following experiment was performed to observe tumor-specific antigens by implanting DMBA pellet into submaxillary gland of rat for inducing salivary gland tumor. After dividing 280 rats into 2 groups, in control group, sham operation was performed on right submaxillary gland and, in experimental group, DMBA pellet (5mg) was implanted into right submaxillary gland. Then proteins from excised submaxillary gland by killing 10 rats every two weeks for 28 weeks were extracted with 3M KCl, and SDS-PAGE and PAS-staining were carried out for biochemical examination. The obtained results were summarized as follows; 1) At 12th week since implantation of DMBA pellet, tumor mass formation was inspected. And dysplasia at 6th week and invasive epidermoid carcinoma at 10th week were observed by microscope. 2) In control group, the weight ratio of both submaxillary glands had no any change, however, in experimental group, the ratio was increased remarkably. And at 28th week after DMBA implantation, there was more than 15 times of differences in weight between control and experimental group. 3) There was no DMBA remnant after 22nd experimental week. 4) In the SDS-PAGE, high molecular protein bands (more than 100 kd) were appeared much, and new prominent protein bands (66, 48, 41.5, 39, 37, 37.5 kd) were appeared after 4th week since DMBA implantation. However, 38, 27, 22kd protein bands were disappeared. 5) In PAS-staining, high molecular proteins were proteins were all glycoproteins and 37.5kd protein was proved as to be glycoprotein. And 38kd glycoprotein was disappeared after 4th week since DMBA implantation.

• Archives of Pharmacal Research
• /
• 제22권4호
• /
• pp.340-347
• /
• 1999

Dendritic cells (DCs) are potent professional antigen-presenting cells (APC) capable of inducing the primary T cell response to antigen. Although tumor cells express target antigens, they are incapable of stimulating a tumor-specific immune response due to a defect in the costimulatory signal that is required for optimal activation of T cells. In this work, we describe a new approach using tumor-DC coculture to improve the antigen presenting capacity of tumor cells which does not require a source of tumor-associated antigen. Immunization of a weakly immunogenic and progressive tumor cocultured with none marrow-derived DCs generated an effective tumor vaccine. Immunization with the cocutured DCs was able to induce complete protectiv immunity against tumor challenges and was effective for the induction of tumor-specific CTL (cytotoxic T lymphocyte) activity. Furthermore, high NK cell activity was observed in mice in which tumors were rejected. In addition, immunization with tumor-pulsed DC s induced delayed tumor growth, but not tumor eradication in tumor-bearing mice. Our results demonstrate that coculture of DCs with tumors generated antitumor immunity due to the NK cell activation as well as tumor-specific T cell. This approach would be used for designing tumor vaccines using DCs when the information about tumor antigens is limited.

• IMMUNE NETWORK
• /
• 제6권2호
• /
• pp.102-110
• /
• 2006

Background: Dendritic cells (DC) are professional antigen-presenting cells in the immune system and can induce T cell response against virus infections, microbial pathogens, and tumors. Therefore, immunization using DC loaded with tumor-associated antigens (TAAs) is a powerful method of inducing anti-tumor immunity. For induction of effective anti-tumor immunity, antigens should be efficiently introduced into DC and presented on MHC class I molecules at high levels to activate antigen-specific $CD8^+$ T cells. We have been exploring methods for loading exogenous antigens into APC with high efficiency of Ag presentation. In this study, we tested the effect of the cationic liposome (Lipofectin) for transferring and loading exogenous model antigen (OVA protein) into BM-DC. Methods: Bone marrow-derived DC (EM-DC) were incubated with OVA-Lipofectin complexes and then co-cultured with B3Z cells. B3Z activation, which is expressed as the amount of ${\beta}$-galactosidase induced by TCR stimulation, was determined by an enzymatic assay using ${\beta}$-gal assay system. C57BL/6 mice were immunized with OVA-pulsed DC to monitor the in vivo vaccination effect. After vaccination, mice were inoculated with EG7-OVA tumor cells. Results: BM-DC pulsed with OVA-Lipofectin complexes showed more efficient presentation of OVA-peptide on MHC class I molecules than soluble OVA-pulsed DC. OVA-Lipofectin complexes-pulsed DC pretreated with an inhibitor of MHC class I-mediated antigen presentation, brefeldin A, showed reduced ability in presenting OVA peptide on their surface MHC class I molecules. Finally, immunization of OVA-Lipofectin complexes-pulsed DC protected mice against subsequent tumor challenge. Conclusion: Our data provide evidence that antigen-loading into DC using Lipofectin can promote MHC class I- restricted antigen presentation. Therefore, antigen-loading into DC using Lipofectin can be one of several useful tools for achieving efficient induction of antigen-specific immunity in DC-based immunotherapy.

• Journal of Gastric Cancer
• /
• 제5권3호
• /
• pp.180-185
• /
• 2005

목적: 정상세포와는 달리 종양세포에서만 비교적 특이적으로 발현되는 것을 tumor specific antigens이라고 하며 대표적인 것은 악성흑색종에서 처음 발견된 MAGE (melanoma antigen)가 있다. 위암조직에서의 MAGE subtype의 발현율은 약 $20{\sim}40%$ 정도로 알려져 있는데 진행성 위암은 전체적으로 예후가 불량하기 때문에 면역치료법과 같은 새로운 치료법을 고려해 볼 수 있다. 본 연구에서는 술 후에 얻은 정상 및 암 조직에서의 MAGE의 발현정도를 각 subtypes에 공통으로 존재하는 유전자를 Primers로 이용하여 조사하였다. 대상 및 방법: 내시경에서 진행성 암으로 진단된 후 수술받은 환자 53명을 대상으로 하였으며, 수술 중 절제된 위에서 정상조직과 암 조직을 얻어 $-70^{\circ}C$에서 보관하였다. 환자는 남자가 35명, 여자가 18명이었고 이들의 평균 연령은 57세였다. 보관된 조직에서 m-RNA를 분리한 후 RT-PCR과 nested PCR로 MAGE의 발현여부를 알아보았다. 기존에 알려진 MAGE gene의 subtypes에 공통으로 존재하는 oligonucleotides를 일차 primers로 이용하여 증폭시켰다. 그 후 또 다른 primers를 이용한 nested RT-PCR을 시행하여 각 조직에서의 발현율을 조사하였다. 결과: 위암환자에서 53예의 암조직 중 13개(24.5%)에서 MAGE gene이 양성으로 나왔고 정상조직에서는 MAGE gene이 모두 음성이었다. 위암의 조직형, ABO type, CEA, CA19-9와 cancer의 위치와는 상관관계가 없었다. 결론: 위암환자의 $20{\sim}30%$에서 MAGE gene이 발현되었으며, 이에 MAGE gene을 이용한 면역치료법의 시도가 필요 할 것으로 생각한다.

• IMMUNE NETWORK
• /
• 제1권1호
• /
• pp.1-6
• /
• 2001

The identification of tumor-specific antigens has represented a critical milestone in cancer diagnosis and therapy. Clinical research in this area for leukemia has also been driven over the past few decades by the hope that surface antigens with restricted tissue expression would be identified. Disappointingly, only a small number of the leukemic antigens identified to date, meet sufficient criteria to be considered viable immunophenotypic markers. In this paper, we nominate anti-JL1 monoclonal antibody as an immunodiagnostic and immunotherapeutic candidate for leukemia. The JL1 molecule appears to be a novel cell surface antigen, which is strictly confined to a subpopulation of limited stages during the hematopoietic differentiation process. Despite the restricted distribution of the JL1 antigen in normal tissues and cells, anti-JL1 monoclonal antibody specifically recognizes various types of leukemia, irrespective of immunophenotypes. On the basis of these findings, we propose JL1 antigen as a tumor-specific marker, which shows promise as a candidate molecule for diagnosis and immunotherapy in leukemia, and one that spares normal bone marrow stem cells.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권18호
• /
• pp.7703-7705
• /
• 2014

Cancer-testis (CT) antigens are a group of tumor-associated antigens with restricted expression in normal tissues except for testis and expression in a wide variety of tumor tissues. This pattern of expression makes them suitable targets for immunotherapy as well as potential biomarkers for early detection of cancer. However, some genes attributed to this family are now known to be expressed in other normal tissues which put their potential applications in immunotherapy and cancer detection under question. Here we analyzed expression of two previously known CT antigens, RHOXF2 and PIWIL2, in AML patients versus normal donors and found no significant difference in the expression of these genes between the two groups. As these two genes showed expression in normal leukocytes, their expression pattern seems to be wider than to be attributed to the CT gene family. Future research should focus on the expression profiles of so called CT antigens to find those with more testis specific expression.