作者: Han, Qinghong ; Miwa, Shinji ; Hayashi, Katsuhiro ; Asano, Yohei ; Kim, Jin Soo ; Igarashi, Kentaro ; Hoffman, Robert M ; Tsuchiya, Hiroyuki ; Li, Shukuan ; Demura, Satoru ; Kimura, Hiroaki ; Kang, Byung Mo ; Higuchi, Takashi ; Yamamoto, Norio ; Mizuta, Kohei ; Morinaga, Sei

BACKGROUND/AIM:

Recent studies have shown that ivermectin, developed as an anti-parasitic drug, has efficacy against several cancer types. Methionine restriction, including the use of recombinant methioninase (rMETase), has been developed to target methionine addiction, a fundamental hallmark of cancer, termed the Hoffman effect. Metastatic colorectal cancer (CRC) is a recalcitrant disease that requires novel and disruptive treatment approaches. The present study aimed to determine the efficacy of ivermectin in combination with rMETase on a CRC cell line compared to normal fibroblasts.

MATERIALS AND METHODS:

The human CRC cell line HCT-116 and normal human fibroblasts Hs27 were seeded at a density of 1,000 cells per well in 96-well plates and cultured overnight at 37°C. After treatment with ivermectin (0.5 μM to 128 μM) or rMETase (0.0625 U/ml to 8 U/ml) for 72 h, cell viability was assessed using the WST-8 reagent to determine the half-maximal inhibitory concentration (IC₅₀) values for ivermectin and rMETase on both cell lines. Using these IC₅₀ values, cell-viability assays for ivermectin alone, rMETase alone, and the combination of ivermectin and rMETase were performed on both cell lines to determine their synergy.

RESULTS:

The IC₅₀ value for ivermectin alone was 4.81 μM and rMETase alone was 0.61 U/ml against HCT-116 colon-cancer cells. The IC₅₀ value for ivermectin alone was 8.67 μM and rMETase alone was 0.67 U/ml against Hs27 normal fibroblasts. In HCT-116 cells, treatment with the combination of ivermectin and rMETase resulted in greater reduction of cell proliferation, compared to treatment with each drug alone; however, no synergy was observed against Hs27 cells.

CONCLUSION:

rMETase and ivermectin showed selective synergistic anti-cancer efficacy against colon-cancer cells, indicating the clinical potential of the combination for metastatic CRC.

2025-06-01·JOURNAL OF GASTROINTESTINAL SURGERY

Enhanced visualization of colonic polyps using a fluorophore-conjugated claudin-1 antibody in a CPC-APC mouse model

Article

作者: Primeaux, Mark ; Hoffman, Robert M ; Liu, Shanglei ; Jaiswal, Sunidhi ; Batra, Surinder K ; Bouvet, Michael ; Talib, Sumbal ; Amirfakhri, Siamak ; Pisegna, Joseph R ; Mohs, Aaron M ; Jih, Lily J ; Singh, Satish K ; Dhawan, Punita ; Cox, Kristin E

BACKGROUND:

Early detection and removal of polyps for primary colon cancer prevention during colonoscopy are still fraught with significant miss rates. In the current study, we determined the ability of claudin-1 (CLDN1) antibodies conjugated to near-infrared fluorophores to target and visualize colonic polyps with high resolution in the CPC-APC mouse colonic polyp model.

METHODS:

CPC-APC mice that developed distal colon polyps at 12 weeks of age were used in the present study. The formation of polyps was confirmed by mouse colonoscopy using the ColoView system (Karl Stortz). For polyp labeling, anti-CLDN1 and control immunoglobulin G (IgG) antibodies were conjugated to IRDye800 and 50, 100, and 150 μg doses were administered intravenouly to CPC-APC mice. Mice were sacrificed at different time points, and colons were harvested for imaging using the LI-COR Pearl Small Animal Imaging System. Polyp-to-background fluorescence intensity ratios (PBRs) were calculated for each polyp. Histology and immunohistochemistry (IHC) were performed on the polyps.

RESULTS:

A total of 9 mice were used in the experiment, with a total of 45 polyps analyzed. The presence of observed polyps on gross examination was confirmed via histology. CLDN1-IRDye800 had a PBR of 7.6 ± 3.9, which was significantly higher than the nonspecific IgG-IRDye800 control (P =.0428). CLDN1-IRDye800 was further analyzed and overall had a similar range of PBR with 50, 100, and 150 μg injections at 72 h and had a statistically significant higher PBR of 8.9 ± 4.2 than the IgG-IRDye800 control (P =.0184) at 150 μg. Adenomatous polyps as small as 1 mm could be identified using CLDN1-IRDye800. Hematoxylin and eosin staining confirmed adenomatous polyps with high-grade dysplasia, and IHC confirmed the expression of CLDN1.

CONCLUSION:

CLDN1-IRDye800 enabled polyp visualization with ultrahigh-resolution fluorescence imaging technology in CPC-APC mice. Polyps as small as 1 mm could be visualized, indicating clinical potential to overcome the current limitations of colonic polyp detection.

2025-06-01·ANTICANCER RESEARCH

Tumor Immunology Visualized in Realtime inIn-vivo-like 3-D Gelfoam^®Histoculture by Color-coded Imaging

Article

作者: Reynoso, Jose ; Bouvet, Michael ; Hoffman, Robert M ; Tome, Yasunori ; Kang, Byung Mo ; Kim, Jin Soo ; Nishida, Kotaro ; Asano, Yohei ; Mizuta, Kohei

BACKGROUND/AIM:

Tumor immunology and immunotherapy have been intensely researched recently, especially with the development of immune checkpoint inhibitors (ICIs). However, only a small percentage of patients respond to ICIs, and this response is limited to a minority of cancer types, such as colon cancer, lung cancer, and melanoma. The aim of the present study was to develop an imageable in-vivo-like in vitro system to directly visualize tumor immunology and immunotherapy in real-time, to further understand tumor immunology and develop improved tumor immunotherapy.

MATERIALS AND METHODS:

Lewis lung carcinoma cells labeled with red fluorescent protein (LLC-RFP) and peripheral blood mononuclear cells labeled with green fluorescent protein (PBMCs-GFP), derived from transgenic GFP mice, were cultured in two dimensions (2-D) on plastic or in three dimensions (3-D) in Gelfoam^® histoculture, using RPMI-1640 culture medium with 10% fetal bovine serum, and 1% penicillin/streptomycin, and with concanavalin-A.

RESULTS:

LLC-RFP cells seeded on Gelfoam^® formed glandular-like structures after 2 days of histoculture. PBMCs-GFP were seeded on Gelfoam^® with LLC-RFP after one day to establish a co-culture. The PBMCs-GFP co-localized with many of the structures formed by the LLC-RFP cells after one day of seeding PBMCs-GFP, suggesting a very specific interaction necessary for an immunological interaction. In contrast, only a few randomized co-localizations of PBMCs-GFP and the LLC-RFP cells were seen on plastic in 2-D culture.

CONCLUSION:

The present results demonstrate a new 3-D co-culture color-coded system to visualize in real-time the interaction of PBMCs and cancer cells using fluorescence color-coded imaging. Future experiments will test drugs that can stimulate immune reactions between the PBMCs and cancer cells.

项与 AntiCancer, Inc. 相关的新闻（医药）

2025-05-09

·今日头条

γδT 细胞疗法力挽狂澜，助肾癌患者转移灶清零，实现2年无癌生存

在癌症治疗的漫漫征程中，每一次突破都承载着无数患者的希望！近年来，γδT细胞犹如一颗闪耀的新星，凭借其独特且强大的免疫特性，强势闯入癌症免疫疗法的研发舞台中心，迅速成为科研人员眼中的 “香饽饽”。如今，多种基于γδT细胞的创新疗法更是如雨后春笋般涌现，纷纷踏入临床试验阶段，为攻克癌症带来了无限可能！《Anticancer Research》就曾报道过一则经典案例：一位肾细胞癌患者在根治术后出现肺部转移，随后接受自体体外活化的γδT细胞输注，并配合低剂量IL-2及唑来膦酸治疗。令人惊喜的是，患者实现完全缓解，而且在之后的两年时间里，无需任何额外治疗，病情始终保持稳定！无疑给众多癌症患者注入了一针强心剂，让我们有理由相信，在不久的将来，越来越多的患者将在这些创新疗法的帮助下，走向康复！ ▲截图源自“anticancer research” 一、Vγ2Vδ2 T 细胞助肾癌肺转移患者，实现完全缓解，斩获2年无瘤生存本例患者是一位61岁的男性，确诊为右侧肾细胞癌，并伴肺转移，此前接受了根治性肾切除术。术后病理显示为透明细胞型肾细胞癌，3级，pT1b分期。随后，患者接受为期三个月的干扰素α（IFN-α）治疗，但CT检查显示肿瘤负荷未见明显变化。在IFN-α洗脱期一个月后，治疗迎来关键转折：患者通过白细胞分离术获取外周血单核细胞（PBMC），并同步静脉注射IL-2与唑来膦酸（持续30分钟），随后输注活化的Vγ2Vδ2 T细胞。令人振奋的治疗效果随之出现：CT影像显示的多发性肺转移灶，在3个疗程后显著缓解，6个疗程后完全消失。更令人惊喜的是，患者在完成最后一个疗程治疗后，已持续2年保持完全缓解（CR）状态，且未接受任何针对肾细胞癌的额外治疗（详见下图）。 ▼下图展示了该患者参与临床试验前、治疗第6个疗程后4个月获得的代表性CT图像 ▲图源“anticancer research”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除这一案例有力证实，基于Vγ2Vδ2T细胞的免疫疗法不仅安全可行，更展现出显著临床价值，为晚期肾细胞癌患者带来全新的治疗希望！二、γ-δT细胞：连接天然免疫与获得性免疫的桥梁，兼具抗肿瘤和抗病毒的双重功效 γδ-T细胞是一类罕见的T细胞亚群，又可分为两个主要的亚群，即Vδ1、Vδ2。由于γ、δ链结构的不同，各亚群的功能也有差异，如Vδ2细胞亚群就具有抗肿瘤、抑制病菌感染的特性。 γ-δT细胞虽然仅占T淋巴细胞的0.5%~5%，但其功能全面、强大，被视为T细胞中的“特种部队”。而且无需抗原提呈细胞参与，即可选择性地识别并杀伤肿瘤细胞、被病菌感染的细胞，最近在新型癌症免疫疗法的开发中引起了相当大的关注。相比其他免疫细胞，γ-δT细胞最独特的优势在于它既有抗肿瘤的功能，同时又具有抗感染的双重作用，是天然免疫与获得性免疫的“桥梁”，在免疫功能的响应中发挥着不可或缺的作用。 ▲图源“cnki”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除三、小编寄语 γδT细胞因具有强大的肿瘤杀伤活性、独特的肿瘤抗原识别能力、卓越的免疫监视特性、易于体外操作等优势，而成为治疗多种癌症的新型候选细胞。值得一提的是，γδT细胞免疫疗法与现有抗癌手段（如手术、化疗和分子靶向药物）的“强强联合”，具有广阔的应用潜力，也是未来抗癌临床研究的关键领域，有望改善癌症患者的预后！想γδT细胞等国内外新兴抗癌疗法更多内容的患者，可以将近期病理检查结果、影像学报告、治疗经历、出院小结等资料，提交至全球肿瘤医生网医学部，进行初步评估或了解详细的入排标准。四、参考资料 [1]Kobayashi H,et al. Complete remission of lung metastasis following adoptive immunotherapy using activated autologous γδ T-cells in a patient with renal cell carcinoma[J]. Anticancer research, 2010, 30(2): 575-579. https://ar.iiarjournals.org/content/30/2/575.long 本文为全球肿瘤医生网原创，未经授权严禁转载

免疫疗法细胞疗法临床结果临床2期

2024-01-29

·BioSpace

AntiCancer Inc. Has Received a New Patent That Revolutionizes Individualized Mouse Models of Human Cancer Patients by Increasing the Patient-tumor Establishment Rate in Mice to Close to 100%

SAN DIEGO--(BUSINESS WIRE)-- AntiCancer Inc. announced it has just received US Patent 11,871,731 that describes a method to increase the rate of establishment of patient tumors in mice to close to 100%. Previously the establishment rates were much lower, in many cases only 10-20% in laboratories around the world. “The new method allows, for the first time, large scale and commercial success of establishing mouse models for each cancer patient to individualize and optimize their cancer therapy, as well as banking their tumors after establishment for future therapy,” said Chihiro Hozumi, co-inventor of the patent and General Manager of AntiCancer’s Japanese subsidiary, AntiCancer Japan. “The new method is especially important as almost all cancer patients can now have their own individualized clinically-concordant PDOX mouse model,” said AntiCancer Senior Mouse-Model Scientist Jose Reynoso. “The new method facilitates the discovery of effective cancer drugs, since many more mouse models of cancer with patient tumors will be available for testing of novel cancer drugs,” said AntiCancer Senior Scientist Qinghong Han. AntiCancer Inc. of San Diego was established in 1984 and is celebrating its 40th anniversary. AntiCancer is a world leader in developing individualized cancer therapy, including contract research, using its proprietary PDOX mouse model which it has developed since 1987, and most closely represents the cancer patient. View source version on businesswire.com: Contacts Qinghong Han, MD all@anticancer.com Source: AntiCancer Inc. View this news release online at:

2023-10-02

·BioSpace

AntiCancer’s PDOX Mouse Model Has Demonstrated High Clinical Concordance Which Will Enable Precise Individualized Chemotherapy of Cancer Patients

SAN DIEGO--(BUSINESS WIRE)-- AntiCancer Inc. of San Diego has announced its PDOX mouse model of human cancer patients has demonstrated high concordance of chemotherapy in the mouse and patient. “This new result means AntiCancer has made the first steps for precise, individualized cancer chemotherapy,” said Qinghong Han, Senior Scientist at AntiCancer Inc. “The PDOX mouse model has the patient’s tumor implanted in the same organ in the mouse as it was in the patient enabling very accurate prediction of chemotherapy outcome for the patient,” said Dr. Han. “AntiCancer’s technique of patient-tumor establishment in mice is close to 100%, making the PDOX model available potentially to all patients,” technique-inventor and AntiCancer-Japan General Manager Chihiro Hozumi said. AntiCancer has published 165 scientific papers on its PDOX model since 1991. The latest paper on clinical concordance of the PDOX model is published in the October 2023 issue of Anticancer Research. AntiCancer Inc., San Diego, is a world leader in mouse models of cancer; small-animal imaging; methionine-restriction treatment of cancer; bacterial therapy of cancer, adult stem cells for regenerative medicine, in vitro assays of cancer therapy, a pioneer in fluorescence-guided surgery, and more, demonstrated in 1200 scientific publications and almost 200 patents. AntiCancer Inc. was founded in 1984. View source version on businesswire.com: Contacts Qinghong Han, MD all@anticancer.com Source: AntiCancer Inc. View this news release online at:

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