• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4037-4043
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• 2012

Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.493-509
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• 2015

Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris$^{(R)}$(anti-CD30-drug conjugate) and Kadcyla$^{(R)}$(anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.15-20
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• 2013

Urinary bladder squamous cell carcinoma (SCC), one of the most common neoplasms in Egypt, is attributed to chronic urinary infection with Schistosoma haematobium (Schistosomiasis). The proto-oncogene c-KIT, encoding a tyrosine kinase receptor and implicated in the development of a number of human malignancies, has not been studied so far in schistosomal urinary bladder SCCs. We therefore determined immunohistochemical (IHC) expression of c-KIT in paraffin sections from 120 radical cystectomies of SCCs originally obtained from the Pathology Department of Suez Canal University (Ismailia, Egypt). Each slide was evaluated for staining intensity where the staining extent of >10% of cells was considered positive. c-KIT overexpression was detected in 78.3% (94/120) of the patients, the staining extents in the tumor cells were 11-50% and >50% in 40 (42.6%) and 54 (57.4%) respectively. The positive cases had 14.9%, 63.8%, 21.3% as weak, moderate and strong intensity respectively. Patients with positive bilharzial ova had significantly higher c-KIT expression than patients without (95.2% vs. 38.9%, P=0.000). Mutation analysis of exons 9-13 was negative in thirty KIT positive cases. The high rate of positivity in SBSCC was one of the striking findings; However, CD117 may be a potential target for site specific immunotherapy to improve the outcome of this tumor.

• 대한의용생체공학회:의공학회지
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• 제13권3호
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• pp.181-188
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• 1992

This paper provides an overview of system analysis of immunology. The theoretical research in this area is aimed at an understanding of the precise manner by which the immune system controls Infec pious diseases, cancer, and AIDS. This can provide a systematic plan for immunological experimentation by means of an integrated program of immune system analysis, mathematical modeling and computer simulation. Biochemical reactions and cellular fission are naturally modeled as nonlinear dynamical processes to synthesize the human immune system! as well as the complete organism it is intended to protect. A foundation for the control of tumors is presented, based upon the formulation of a realistic, knowledge based mathematical model of the interaction between tumor cells and the immune system. Ordinary bilinear differential equations which are coupled by such nonlinear term as saturation are derived from the basic physical phenomena of cellular and molecular conservation. The parametric control variables relevant to the latest experimental data are also considered. The model consists of 12 states, each composed of first-order, nonlinear differential equations based on cellular kinetics and each of which can be modeled bilinearly. Finally, tumor control as an application of immunotherapy is analyzed from the basis established.

• Tuberculosis and Respiratory Diseases
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• 제57권4호
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• pp.336-344
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• 2004

연구배경 : 폐암에 대한 거의 대부분의 면역 치료는 실패하였는데, 이는 폐암 자체에 존재하는 면역 억제 기전을 극복하지 못한데 기인하는 것으로 판단된다. Uteroglobin (UG, CCSP)은 항염증 등의 활성을 보인다. 방 법 : A549에 Ad-UG을 처리하고, 상층액의 $PGE_2$ 농도를 측정하였다. RPMI 1640, A549 배양액과 UG 혹은 COX-2 억제제인 NS-398을 처리 후 얻은 폐암세포주 상층액으로 PBMC를 배양 후 Th 1 type cytokines과 Th 2 type cytokines의 농도를 측정하였다. 결 과 : $PGE_2$는 UG이 발현되는 세포주에서 감소하였다. 폐암 세포 배양 배지로 키운 면역 세포의 cytokines가 증가하는 양상을 보였으나, UG등을 처리한 비소세포 폐암주의 배양액은 PBMC의 면역 반응을 정상적으로 유도하였다. 결 론 : 비소세포폐암주 배양액은 PBMC의 면역 반응을 비정상적으로 유도하지만, UG은 $PGE_2$의 분비를 억제함으로써, PBMC의 면역 반응을 강화시킨다.

• 대한의용생체공학회:학술대회논문집
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• 대한의용생체공학회 1991년도 춘계학술대회
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• pp.82-85
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• 1991

Cell kinetics and the chemical mass action principle formulate the basis of immune system dynamics which may be synthesized mathematically as cascades of bilinear systems which are connected by nonlinear nondynamical terms. In this manner, a model for cell-mediated immune response (CMI) to tumor antigens and debris is developed. We also consider parametric control variables relevant to the latest experimental data, i.e., sigmoidal dose-response relationship and Michaelis-Menten dynamics. The preliminary results show that the parametric control variable is important in the destruction of tumors. As well as that, the exacerbation theory is a good method for tumor treatment. Finally, tumor control as an application of immunotherapy is analyzed from the basis established above.

• 대한의생명과학회지
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• 제18권3호
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• pp.210-217
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• 2012

Oncolytic viral vectors have shown good candidates for cancer treatment but have many limitations. To improve the therapeutic potential of oncolytic vaccinia virus, we developed a recombinant vaccinia virus expressing the 4-1BBL co-stimulatory molecule or CCL21. 4-1BBL and CCL21 expression was identified by FACS analysis and immunoblotting. rV-4-1BBL vaccination shows significant tumor regression compared to rV-LacZ, but rV-CCL21 shows rapid tumor growth compared to rV-LacZ in the poorly immunogenic B16 murine melanoma model. 4-1BBL expression resulted in the increase of the number of CD8+ T cells and especially the increase of effector (CD62L-CD44+) CD8+ T cells. These data suggest 4-1BBL may be the potential target for enhancement of tumor immunotherapy.

• Nuclear Medicine and Molecular Imaging
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• 제41권1호
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• pp.1-8
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• 2007

This review discusses the production of alpha-particle-emitting radionuclides in radioimmunotherapy. Radioimmunotherapy labeled with alpha-particle is expected to be very useful for the treatment of monocellular cancer (e.g. leukemia) and micrometastasis at an early stage, residual tumor remained in tissues after chemotherapy and tumor resection, due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha particle. Despite of the expected effectiveness of alpha-particle in radioimmunotherapy, its clinical research has not been activated by the several reasons, shortage of a suitable a-particle development and a reliable radionuclide production and supply system, appropriate antibody and chelator development. Among them, the establishment of radionuclide development and supply system is a key factor to make an alpha-immunotherapy more popular in clinical trial. Alpha-emitter can be produced by several methods, natural radionuclides, reactor irradiation, cyclotron irradiation, generator system and elution. Due to the sharply increasing demand of $^{213}Bi$, which is a most promising radionuclide in radioimmunotherapy and now has been produced with reactor, the cyclotron production system should be developed urgently to meet the demand.

• 대한물리치료과학회지
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• 제7권2호
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• pp.439-457
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• 2000

The causes, risk factors and sequelae of mastectomy were studied, and the physical therapy approaches on post-mastectomy was discussed in this study. It was found that the patients taken mastectomy have experienced pins and needles in muscle, weakening of muscle, pains, deterioration of motion in joint region and activities of daily living, psychiatric sequelae, and etc even after the conservertive therapies like the chemical therapy, radiotherapy, immunotherapy, and hormone therapy. However, few study on the physical therapy approaches for patients with breast cancer has been carried in Korea at present. The followings were proposed as the physical therapy approaches. 1. Shoulder joint motion approach to relax the limit of range of motion 2. Control of breathing exercise for dealing with removal of the pectorailis muscle 3. Method to reduce the edema of arms for tackling the cut of lymph node 4. Method to reduce pains, pins and needles 5. Support home exercise program after discharging from hospital, sexual life and pregnancy, and activities of daily living training method.

• 응용통계연구
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• 제2권2호
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• pp.27-35
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• 1989

최근 암의 면역치료 요법에 사용이 활발히 시도되고 있는 IL-2(Interleukin-2)의 역가를 측정하는 문제를 통계적 모형을 통하여 정립하고 그 모형하에서 모수의 함수로 표현되는 역가의 추론과정을 연구하였다. 표준시료와 비교하여, 환자로부터 얻은 미지의 시료의 역가를 구하기 위하여 선형모형을 제시하고 베이지안 기법을 사용하여 계수들의 함수로 나타내지는 역가의 신뢰구간을 구하였으며 실제 데이타에 적용하여 보았다.