Ekaterina Dadachova

University of Saskatchewan | U of S · College of Pharmacy and Nutrition

Introduction: : Corona Virus Disease of 2019 (COVID-19) pandemic has renewed interest in monoclonal antibodies for treating infectious diseases. During last two decades experimental data has been accumulated showing the potential of radioimmunotherapy (RIT) of infectious diseases. In addition, COVID-19 pandemic has created a novel landscape for op...

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse...

Progress in prognostic factors, treatments, and outcome for both canine and human osteosarcoma (OS) has been minimal over the last three decades. Surface overexpression of the cation independent mannose-6-phosphate/insulin-like growth factor receptor type 2 (IGF2R) has been proven to occur in human OS cells. Subsequently, radioimmunotherapy (RIT) t...

Radiation damage is associated with inflammation and immunity in the intestinal mucosa, including gut microbiota. Melanin has a unique capacity to coordinate a biological reaction in response to environmental stimuli, such as radiation exposure. Thus, melanin and melanized microbes have potential to be used for mitigation of injury induced by radia...

Objective: Positron emission tomography (PET) imaging is a powerful non-invasive method to determine the in vivo behavior of biomolecules. Determining biodistribution and pharmacokinetic (PK) properties of targeted therapeutics can enable a better understanding of in vivo drug mechanisms such as tumor uptake, off target accumulation and clearance....

Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies into standard of care...

The field of radiation countermeasures is growing, however, currently there are no effective and non-toxic compounds which could be administered orally to the individuals post exposure to high doses of ionising radiation. The pigment melanin is ubiquitous through all kingdoms of life and provides selective advantage under radiation stress through i...

COVID-19 pandemic has heightened the interest toward diagnosis and treatment of infectious diseases. Nuclear medicine with its powerful scintigraphic, single photon emission computer tomography (SPECT) and positron emission tomography (PET) imaging modalities has always played an important role in diagnosis of infections and distinguishing them fro...

Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human societ...

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and potential treatment of biofilm-related infections. Here, we show that m...

Background: Osteosarcoma (OS) has an overall patient survival rate of ~70% with no significant improvements in the last two decades, and novel effective treatments are needed. OS in companion dogs is phenotypically close to human OS, which makes a comparative oncology approach to developing new treatments for OS very attractive. We have recently c...

Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here, we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human societ...

Mars exploration motivates the search for extraterrestrial life, the development of space technologies, and the design of human missions and habitations. Here we seek new insights and pose unresolved questions relating to the natural history of Mars, habitability, robotic and human exploration, planetary protection, and the impacts on human society...

p>Background: Bone marrow transplantation, ex vivo gene therapies targeting hematological disorders, and other forms of adoptive cell therapies (ACT) require complete or partial removal of the host immune cells by a process called conditioning. This is usually accomplished with total body irradiation (TBI) or chemotherapy, but both modalities can r...

Etiological and genetic drivers of osteosarcoma (OS) are not well studied and vary from one tumor to another; making it challenging to pursue conventional targeted therapy. Recent studies have shown that cation independent mannose-6-phosphate/insulin-like growth factor-2 receptor (IGF2R) is consistently overexpressed in almost all of standard and p...

Implant-associated Staphylococcus aureus infections are difficult to treat because of biofilm formation. Bacteria in a biofilm are often insensitive to antibiotics and host immunity. Monoclonal antibodies (mAbs) could provide an alternative approach to improve the diagnosis and/or treatment of biofilm-related infections. Here we show that mAbs targ...

Drug resistance presents an enormous problem in cancer which results in poor overall survival of cancer patients. Osteosarcoma and pancreatic adenocarcinoma are two examples of cancers where no meaningful progress in improving the survival of patients with metastatic disease has been achieved in the past 25 years. Osteosarcoma is a primary cancer o...

Purpose Despite the availability of new drugs, many patients with acute myeloid leukemia (AML) do not achieve remission and outcomes remain poor. Venetoclax is a promising new therapy approved for use in combination with a hypomethylating agent or with low‐dose cytarabine for the treatment of newly diagnosed older AML patients or those ineligible f...

Melanized fungi have been isolated from some of the harshest radioactive environments, and their ability to thrive in these locations is in part due to the pigment melanin. Melanin imparts a selective advantage to fungi by providing a physical shield, a chemical shield, and possibly a signaling mechanism. In previous work we demonstrated that protr...

Melanoma incidence continues to rise, and while therapeutic approaches for early stage cases are effective, metastatic melanoma continues to be associated with high mortality. Immune checkpoint blockade (ICB) has demonstrated clinical success with approved drugs in cohorts of patients with metastatic melanoma and targeted radionuclide therapy strat...

Purpose Despite the availability of new drugs, many patients with acute myeloid leukemia (AML) do not achieve remission and outcomes remain poor. Venetoclax is a promising new therapy approved for use in combination with a hypomethylating agent or with low dose cytarabine for the treatment of newly diagnosed older AML patients or those ineligible f...

Chimeric antigen receptor (CAR) T cell therapies, and adoptive cell therapy (ACT) in general, represent one of the most promising anti-cancer strategies. Conditioning has been shown to improve the immune homeostatic environment to enable successful ACT or CAR-T engraftment and expansion in vivo following infusion, and represents potential point of...

Background: With the limited options available for therapy to treat invasive fungal infections (IFI), radioimmunotherapy (RIT) can potentially offer an effective alternative treatment. Microorganism-specific monoclonal antibodies have shown promising results in the experimental treatment of fungal, bacterial, and viral infections, including our rec...

Background: Widespread use and misuse of antibiotics have led to a dramatic increase in the emergence of antibiotic resistant bacteria, while the discovery and development of new antibiotics is declining. This has made certain implant-associated infections such as periprosthetic joint infections, where a biofilm is formed, very difficult to treat....

Background Implant associated infections such as periprosthetic joint infections are difficult to treat as the bacteria form a biofilm on the prosthetic material. This biofilm complicates surgical and antibiotic treatment. With rising antibiotic resistance, alternative treatment options are needed to treat these infections in the future. The aim of...

Stress is a normal part of life for fungi, which can survive in environments considered inhospitable or hostile for other organisms. Due to the ability of fungi to respond to, survive in, and transform the environment, even under severe stresses, many researchers are exploring the mechanisms that enable fungi to adapt to stress. The International S...

Introduction Radiolabeled CD45 antibodies have demonstrated clinical promise as targeted conditioning agents prior to bone marrow transplant (BMT) as a better tolerated and potentially more effective alternative to chemotherapy and/or total body irradiation myeloablative conditioning regimens. CD45 is expressed on all immune cells, including hemato...

Invasive fungal infections (IFI) cause devastating morbidity and mortality, with the number of IFIs more than tripling since 1979. Our laboratories were the first to demonstrate that radiolabeled microorganism-specific monoclonal antibodies are highly effective for treatment of experimental fungal, bacterial and viral infections. Later we proposed...

Background: cART has significantly improved the life expectancy of people living with HIV (PLWH). However, it fails to eliminate the long-lived reservoir of latent HIV-infected cells. Radioimmunotherapy (RIT) relies on antigen-specific monoclonal antibodies (mAbs) for targeted delivery of lethal doses of ionizing radiation to cells. Previously, we...

Immunotherapy has changed the oncology landscape during the last decade and become standard of care for several cancers. The combinations of immunotherapy with other treatment modalities are also being investigated. One of the challenges to investigate such combinations is to identify suitable mouse models for the pre-clinical experiments. In the p...

Introduction: Radiolabeled CD45 antibodies have demonstrated clinical promise as targeted conditioning treatments prior to bone marrow transplant (BMT) as a better tolerated and potentially more effective alternative to harsh chemotherapy and/or total body irradiation regimens for myeloablative conditioning. CD45 is expressed on all immune cells, i...

Black fungi withstand extreme stresses partly due to the presence of melanin. Melanin is associated with structural integrity and resistance to chemical and radiation stress. This results in improved health and fitness, specifically in extreme conditions. Our goal was to exploit the radiation sensing nature of melanized fungus in order to develop a...

Nearly all cases of cervical cancer are initiated by persistent infection with high-risk strains of human papillomavirus (hr-HPV). When hr-HPV integrates into the host genome, the constitutive expression of oncogenic HPV proteins E6 and E7 function to disrupt p53 and retinoblastoma regulation of cell cycle, respectively, to favor malignant transfor...

Osteosarcoma (OS) represents 3.4% of all childhood cancers with overall survival of 70% not improving in 30 years. The consistent surface overexpression of insulin-like growth factor-2 receptor (IGF2R) has been reported in commercial and patient-derived xenograft (PDX) OS cell lines. We aimed to assess efficacy and safety of treating PDX and commer...

Scope: Melanin is an ancient and unique pigment that can be found in all phyla of the fungi kingdom. The presence of melanin imparts a selective advantage to fungi promoting survival and cellular fitness. Selective growth of melanized fungi in extreme locations with high levels of ionizing radiation such as the damaged nuclear reactor at Chernobyl...

Melanoma is a cancer with increasing incidence and there is a need for alternatives to immunotherapy within effective approaches to treatment of metastatic melanoma. We performed comparative radioimmunotherapy (RIT) of experimental B16-F10 melanoma with novel humanized IgG to melanin h8C3 labeled with a beta emitter, 177Lu, and an alpha-emitter, 21...

Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for >90% of pancreatic malignancies, and has median survival of <6 months. There is an urgent need for diagnostic and therapeutic options for PDAC. Centrin1 (CETN1) is a novel member of Cancer/Testis Antigens, with a 25-fold increase of CETN1 gene expression in PDX from PDAC patients. Th...

Acute myeloid leukemia (AML) is a complex hematological disease often occurring in older patients. While a number of new targeted therapies have been recently approved, patient outcomes remain poor. In the US, about 19,520 new cases AML occur annually and approximately 10,670 will die from the disease. Venetoclax is a promising new targeted therapy...

Daratumumab is an anti-CD38 directed monoclonal antibody approved for the treatment of multiple myeloma (MM) and functions primarily via Fc-mediated effector mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell cytotoxicity (ADCC), antibody-dependent cellular phagocytosis, and T-cell activation. However, not all patie...

Lymphodepletion, using chemotherapy such as fludarabine and cyclophosphamide (flu/cy), is recognized as a critical step to create a favorable immune homeostatic environment in patients prior to adoptive cell therapy (ACT) or CAR-T. However, flu/cy is a cytotoxic and non-specific regimen that some patients may not be able to tolerate and is also cor...

Modelling the biokinetics of radionuclide excretion or retention is important in nuclear medicine and following accidental/malicious radioactivity releases. Sums of discrete exponential decay rates are often used, but we hypothesized that continuous probability distributions (CPD) of decay rates can describe the data more parsimoniously and robustl...

(1) Background: Monoclonal antibodies are used in the treatment of multiple conditions including cancer, autoimmune disorders, and infectious diseases. One of the initial steps in the selection of an antibody candidate for further pre-clinical development is determining its pharmacokinetics in small animal models. The use of mass spectrometry and o...

Prior to a patient receiving a dose of an adoptive cell transfer such as engineered autologous or allogeneic CAR-T cells, it is common to perform a lymphodepletion step often using high dose chemotherapy. This process is considered important to create sufficient space in the immune microenvironment, e.g. bone marrow, to allow the transferred cells...

Background Children less than 1 year of age are commonly colonized with toxin-producing C. difficile, but appear to be immune to the associated colitis. Animal studies suggest that young infants lack receptors for C. difficile toxin, though this has never been documented in humans. Methods Tissue from infants (<6 months) and adults > 21 years were...

Despite living organisms are not exposed to acute ionizing radiation under natural conditions, some exhibit a high radiation resistance. Understanding this phenomenon is important for assessing the impact of radiation-related accidents, occupational exposures and space missions. In this context, in this study we analyzed the effect of gamma rays on...

In the past several decades, many antimicrobial agents have been used in treating different fungal, bacterial, and viral infections. However, these agents have faced challenges such as pronounced side-effect profiles and pathogen resistance. In addition, a cure for many chronic infections such as human immunodeficiency virus (HIV) has not been achi...

Melanins are ubiquitous in nature, yet their functions remain poorly understood because their structures and properties elude characterization by conventional methods. Since many of melanins’ proposed functions (e.g., antioxidant, pro-oxidant and radical scavenging) involve an exchange of electrons, we developed an electrochemical reverse engineeri...

The BIOMEX (BIOlogy and Mars Experiment) is part of the European Space Agency (ESA) space mission EXPOSE-R2 in Low-Earth Orbit, devoted to exposing microorganisms for 1.5 years to space and simulated Mars conditions on the International Space Station. In preparing this mission, dried colonies of the Antarctic cryptoendolithic black fungus Cryomyces...

Radioimmunotherapy offers an effective way to direct ionizing radiation to cancer cells through attachment of radionuclides to antibodies while limiting negative effects of off-target irradiation. This, however, requires effective facile methods for attachment of therapeutic radionuclides onto antibodies. Herein, the authors report their efforts in...

Daratumumab is a human cytolytic antibody specific for CD38 that is used clinically for treatment of patients with multiple myeloma (MM). Current therapeutic regimens require multiple injections over months of treatment. Increasing the potency of daratumumab to shorten the length of treatment would be beneficial. ²²⁵Ac is an alpha-particle emitting...

Objective: The demand for the alpha-emitting radionuclide Actinium-225 (225Ac) for use in radionuclide therapy is growing. Producing 225Ac using high energy linear accelerators, cyclotrons or photoinduction could increase its supply. One potential problem with accelerator produced 225Ac using Thorium-232 targets is the presence in final product of...

Metastatic melanoma remains difficult to treat despite recent approvals of several new drugs. Recently we reported encouraging results of Phase I clinical trial of radiolabeled with188Re murine monoclonal IgM 6D2 to melanin in patients with Stage III/IV melanoma. Subsequently we generated a novel murine IgG 8C3 to melanin. IgGs are more amenable to...