R&D Project

Kineto Lab Ltd. develops unique methods to be used along the preclinical drug discovery pipeline to identify and validate new drug targets and to predict in vivo toxicity of anticancer drugs. The company’s experience in various research grant projects, such as Horizon 2020, the ever biggest research and innovation program of the European Community gives solid scientific basis to offer efficient service in research, development and screening of drug candidates.

• Development of detection method for circulating endothelial progenitor cells This angiogenesis related project has been successfully completed laying down the principles of developing a detection method for enumeration circulating endothelial progenitor cells. Angiogenesis and vasculogenesis, development of blood vessels are essential steps in the growth of a tumor

• Peptide-Drug Conjugates for Targeted Delivery in Tumor Therapy Kineto Lab is member of the ”MAGIBULLET” international research consortium built for studying the application of drug conjugates in selective tumor therapy.

• Development of Diagnosis and Therapy of RASopathys

• Development of biomedical research and service capacity and explore new types of anti-cancer therapeutic solutions

 

Development of detection method for circulating endotherial progenitor cells (EPCs)

Growth of new blood vessels is required for various pathological processes. Tumor growth and regeneration of hypoxic post-infarction tissues are also dependent on angiogenesis/vasculogenesis, a process which can be achieved through the incorporation of endothelial progenitor cells (EPCs) into the endothelial tube of novel blood capillaries. Based on several observations, the circulating levels of these cells are associated with the severity of the given disease. In line with that, enumeration of EPC numbers can help to assess disease progression, therapeutic efficacy and prognosis. According to recent scientific results, the aim of the project is to develop a technique and, moreover, an own “diagnostic kit” for the detection and enumeration of EPCs.

ID: INNO_08_KM-KLABIN08
2008-2009

no. Ep14168842 2010-2012

HORIZON 2020: European Training Network - MAGICBULLET

Peptide-Drug Conjugates for Targeted Delivery in Tumor Therapy Many tumor cells are characterized by the overexpression of certain antigens. Molecules that specifically recognize these structures are suitable as homing devices in tumor therapy. Conjugates of anticancer drugs with such a delivery vector targeting tumors would be a "magic bullet" according to the Nobel laureate Paul Ehrlich. Three antibody-drug conjugates (ADC) have already been approved for anticancer therapy. However, ADC have e.g. limitations with respect to tumor penetration, high manufacturing costs, and require challenging conjugation chemistry. Peptide-drug conjugates can have a high drug loading, easily penetrate tissue, and can be easily prepared in a homogenous form with straightforward and well-defined conjugation chemistry.

The focus of the ETN MAGICBULLET is on chemistry-driven approaches toward conjugates between peptides (delivery vectors) that recognize tumors and anticancer drugs (payloads or warheads) in order to selectively fight cancer, a topic with a high demand of research activities. The ETN allows to develop and validate an array of new peptide-drug conjugates combining either known tumor-specific peptides or newly discovered tumor-homing peptides with potent cytotoxic drugs. The tumor-selective peptides are designed for cellular uptake mediated either by endocytosis or by cell-penetrating peptides. The consortium of the ETN MAGICBULLET covers tumor biology, biochemistry, pharmacology, synthetic chemistry, medicinal chemistry, spectroscopy, conformational analysis, and computational chemistry. The training program focuses on multidisciplinary research to explore and validate molecular targets for innovative treatment or investigations on the molecular mechanisms in organ-specific metastatic growth processes. It aims at scientific multilingualism and relies e.g. on concerted learning, a combination of introductory training, hands-on learning "on the bench", teaching by peers, and training in additional skills.

The ETN MAGICBULLET is a tool that can

• identify, modify, and validate tumor-selective peptides for known and new cell surface receptor targets (e.g. integrins, VEGFR, cadherins);

• study different linker systems for release of the anticancer payloads at the appropriate site;

• conjugate known and new anticancer agents or drugs to tumor-selective peptides;

• investigate the biological activity in vitro and in vivo to demonstrate their efficacy.

The combination of an array of tumor-selective peptides targeting different receptors and different uptake mechanisms with diverse antitumor drugs acting on different cellular targets is a powerful strategy to minimize potential risks and increase the efficacy. Because the number of receptors on tumor cells is limited, the combination of different target peptide–drug conjugates may enhance the bioactivity. The influence of the treatment schedule of such combination therapy on the antitumor activity will also be evaluated.

MAGICBULLET grant agreement No 642004. 2015-2018 www.magicbullet.de

NVKP-16: Development of Diagnosis and Therapy of RASopathys (RASopátiák diagnosztikájának és terápiájának fejlesztése)

KRAS is one of the most frequently mutated oncogene in human cancer with an outstanding incidence rate among the most prevalent cancers such as colon and rectum cancer (40%), lung adenocarcinomas (30%) and pancreatic cancer (80%). Moreover, with smaller frequency, other tumor types (myeloma multiplex, head and neck- and breast cancer) display KRAS mutations as well. KRAS mutant human cancers are more aggressive and less sensitive to classical chemotherapeutic agents.

In clinical oncology the new paradigm is the introduction of the molecular targeted therapies exploiting the characteristic genetic alterations of the tumors which is frequently mutation of oncogenes. However, the efficacy of targeted therapies (i.e. anti-EGFR agents) is critically determined by the KRAS mutational status of the tumor, as mutated KRAS leads to resistance to these expensive therapies. Therefore, the mutant oncogenic KRAS in human cancer emerged as arguably the most outstanding issue in clinical oncology that should guide the future of R&D activities.

KFI_16: Development of biomedical research and service capacity and explore new types of anti-cancer therapeutic solutions

In this project, KINETO Lab intends to expand its existing tissue culture and animal-based infrastructure so that it can continually be able to isolate larger amount of antibodies several times a year, from the hybridomas created by its own earlier development or from its cells from its academic and industrial partners. The antibodies so obtained are then marketed in various technical solutions (laboratory diagnostic kits, molecular biology reagents, immunohistochemical techniques, etc.).

Testing of new active substances, including therapeutic antibodies, requires the use of better preclinical models. These include molecular biology methods, cell and tissue culture techniques, and animal experiments. This is also the case in oncology. Patient-derived tumor xenografts (PDTX), when implanting a direct surgical sample into specific mice, represent a much better representation of the original tumor because of not only the tumor cells but also their environment are transplanted. The second major objective of the project is to develop such specific models from the least manageable tumor types, subsequent basic and R & D research.

In addition, thirdly, with the help of the models, KINETO Lab develops new types of antibodies that are specifically active in tumor vessels, for diagnostic and therapeutic use. Identification of endothelial markers is a novel therapeutic target that can reduce the side effects of anticancer treatments and increase their effectiveness on tumors.