National Intelligence Service

As the parties concerned seem to be finally groping for the possibility of negotiating a new peace system to replace the old one of armistice in the Korean peninsula, it may be worthwhile to look at the Political Conference on Korea which was held in Geneva over forty years ago. To begin with, this was the first major international conference in which the two Koreas participated as sovereign states.1 This was not limited to formalities. Each, and particularly the Republic of Korea, was an important element in terms of substance throughout the Conference from the very beginning to its termination in its organization, negotiations and conclusion.2 More important, the Conference was the first and last occasion at which the two Koreas participated in a discussion of the unification of Korea together with the leading world powers. The Conference was also the last major occasion on which the Korean problem was discussed in the context of the international order created in the aftermath of the second world war. In other words, it was the last time the major powers in charge of the post-second world war problems dealt with Korean affairs. In particular, the British Commonwealth intervened for the last time in the discussion of Korean problems. Perhaps it was also the last opportunity for Britain to play a hand in international affairs as a world power.3 On the other hand, it also presented the opportunity for the opening of a new era in international politics: the communist regime in China, established through years of civil and anti-Japanese war, was finally making a debut in the international arena on the strength of its successful resistance to the major western powers on the battlefields of Korea. Of course, the USA tried not to recognize the international status of China. However, it was obvious that nobody could deny for long the entry of China into international politics as a power on its own. For the time being, however, the overwhelming influence of the USA suppressed this, at least below the surface. What was strange about this Conference was that nobody, including the actual participants themselves, seriously thought that it would solve any problems. As expected, the Conference ended without any progress being made. Nevertheless, Chou En-lai remarked when the Conference was over that

El algodón (Gossypium hirsutum L.) ha perdido variabilidad debido a su proceso de domesticación. Por esta razón, es necesaria la caracterización molecular y fenotípica de nuevos materiales para los programas de mejoramiento genético de esta especie. El objetivo de este trabajo fue caracterizar la variabilidad de 18 accesiones de tres orígenes geográficos Argentina, Estados Unidos y China por características genéticas y fenotípicas. Los materiales pertenecen al Banco de germoplasma de INTA y se utilizan en el programa de mejoramiento. Para el estudio genético se utilizaron 16 pares de oligonucleòtidos microsatélites. En la caracterización fenotípica se utilizaron variables asociadas al mapeo en dos campañas agrícolas (2015/2016 y 2016/2017) realizadas en el campo de INTA EEA Sáenz Peña. Los resultados genéticos mostraron valores medios/altos de polimorfismo (62,22%) y en el dendrograma se observaron dos grupos; uno representado por Stoneville 474 (Estados Unidos) y ocho genotipos de China y un segundo grupo formado por Deltapine 16 (Estados Unidos), los genotipos de Argentina y un genotipo de China. Los resultados fenotípicos en un análisis multivariado de Componentes Principales entre campañas agrícolas presentaron diferencias significativas, mientras que fueron no significativas entre los diferentes orígenes geográficos. Se concluye que existe uniformidad en los caracteres morfológicos en los tres orígenes geográficos y diferenciación genética a partir del análisis molecular siendo las accesiones BGSP 756, BGSP 767 y BGSP 783 de China las que presentaron mayores distancias con respecto a los materiales de Argentina y Estados Unidos; justificando la introducción de germoplasma de origen de China al programa de mejoramiento de INTA.

Abstract CD47, a broadly expressed transmembrane glycoprotein, interacts with SIRPα to inhibit macrophage-mediated phagocytosis. Its overexpression on cancer cells is associated with poor prognosis, making the CD47-SIRPα axis a promising target for cancer immunotherapy. While blocking this pathway enhances macrophage-driven anti-tumor responses, clinical translation is hindered by challenges such as hematological toxicity and rapid drug clearance due to CD47 expression on normal cells, including red blood cells.IMC-002, a fully human IgG4 monoclonal antibody targeting CD47, was screened for an optimized affinity to balance therapeutic efficacy and safety. Comparative studies with Hu5F9 and 13H3 demonstrated IMC-002’s enhanced selectivity and unique binding profile. In a tumor-RBC co-culture system, IMC-002 exhibited superior binding to CD47+ tumor cells while showing significantly reduced binding to normal cells, including RBCs, platelets, and CD3+ immune cells, compared to Hu5F9. The tumor selectivity and lack of binding to CD47 on RBCs by IMC-002 appear to result from differences in its binding site. Studies investigating the roles of CD47 clustering, Rh complex, Integrin β1, lipid rafts, and glycosylation revealed that O-glycosylation significantly influences IMC-002’s selective binding to CD47. Antibody structure simulations and antigen binding docking analyses confirmed that IMC-002 engages distinct epitopes and adopts a unique binding orientation compared to Hu5F9. Supporting this mechanism, enzymatic removal of O-glycans on RBCs in vitro increased IMC-002 binding, and in-silico epitope mapping identified an O-glycosylation site within the predicted binding region. We evaluated the therapeutic potential of IMC-002 in various solid tumor models through both in vitro and in vivo studies. In vitro functional assays demonstrated that IMC-002 significantly enhanced macrophage-mediated phagocytosis of tumor cells, both as a monotherapy and in combination with standard of care (SoC) treatment. In vivo, IMC-002 exhibited dose-dependent anti-tumor activity in mouse models of triple-negative breast cancer (TNBC), hepatocellular carcinoma (HCC), and biliary tract cancer (BTC). Furthermore, in non-human primates, IMC-002 was well-tolerated, with no hematological toxicity observed at doses up to 100 mg/kg, and exhibited a pharmacokinetic profile consistent with typical therapeutic antibodies. In conclusion, IMC-002 demonstrated exceptional efficacy and safety, attributed to its unique binding site and mechanism of action. These findings provide strong support for its clinical development as a cancer therapeutic. Phase 1a trials confirmed IMC-002's superior safety profile, and ongoing Phase 1b trials are evaluating its efficacy in combination with standard-of-care therapies in patients with HCC and TNBC. Citation Format: Jiyea Choi, Ji-Eun Park, A-Ra Jeon, Heewook Shin, Yeonsun Yu, HyeHyeon Jang, Hyesun Lee, Jiyoung Yoon, Sung Ho Kim, Heung Tae Kim. Development of IMC-002, a next-generation anti-CD47 mAb: an affinity optimized antibody with enhanced safety and therapeutic efficacy in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4789.