Almost 800,000 PLN from NCBiR for research on lymphomas

The competition of the National Centre for Research and Development included application projects submitted under the Smart Growth Operational Programme 2014-2020. The project of the Institute of Immunology and Experimental Therapy in Wrocław (leader) conducted together with scientists from the Wrocław University of Environmental and Life Sciences and the Vet Planet company was rated the highest and awarded 2,333,408.75 PLN for its implementation. This is the next stage of joint activities of immunologists and scientists from Wrocław veterinary medicine, started almost 10 years ago, and concerning research on canine leukaemias and lymphomas, diagnostics of these diseases and treatment options.

Prof. Andrzej Rapak from the Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in Wrocław talks about many years of cooperation with scientists from the Faculty of Veterinary Medicine of the UPWr: - We started with joint grants from the National Science Centre. Back then, the project was about developing canine leukaemia and lymphoma cell lines for research, testing different compounds, and finding those that have therapeutic effects. As part of the first joint grant from the National Science Centre, we were able to obtain monoclonal antibodies against the canine leukaemia line. The next step in the research was a grant under the Tango 2 competition – implemented as a joint project of NCN and NCBiR in terms of application research. In the application submitted this year by a team of researchers from the Institute of Immunology, UPWr and Vet Planet, it was emphasized that lymphoid diseases – leukaemias and lymphomas – account for approximately 30% of all diagnosed types of cancer in dogs. The most common are type B non-Hodgkin lymphomas, analogous to human non-Hodgkin lymphomas (NHL) – they constitute about 20% of all canine cancers and 85% of lymphoid cancers.

- Most procedures, i.e. diagnosis and treatment regimens for acute myeloid and lymphoblastic leukaemias in dogs are based on the guidelines for human leukaemia therapy. Their disadvantage is low specificity with high side effects, but also high costs, which, with the privatization of veterinary treatment, is a burden on the budgets of most dog owners – admits prof. Arkadiusz Miążek, project manager, head of the Centre for Genetic Engineering at the University of Environmental and Life Sciences in Wrocław. Participating in the project, together with prof. Miążek, are prof. Aleksandra Pawlak, Anna Urbaniak PhD and Aleksandra Tabiś, a veterinarian.

Veterinarians admit that the introduction of a test which would be simple, quick and easy to perform in a veterinary clinic, would simplify and speed up the diagnostic process. Hence the goal of the winning project – creation of a set of simple and quick test strips allowing precise determination of the type of haematological disease. Hence the importance of the cooperation with Vet Planet, which has decided to produce a trial series of the tests – they will go to veterinary surgeries, where their effectiveness will be checked by doctors who work with four-legged patients on a daily basis.

- The tests are similar to pregnancy tests. There are test fields with lines in a cassette. After a biological sample from the enlarged lymph node is collected from the dog, it is transferred to the test cassette. Our innovation is that we will not only detect whether we are dealing with a cancer, but also, what is important for the therapy, we will be able to tell what type of lymphoma it is, whether it comes from type B or T cells – explains prof. Miążek.

However, this is not the only goal – as a result of the research carried out so far, scientists from the Polish Academy of Sciences and UPWr have developed a method to obtain two monoclonal antibodies B5 and E11 that recognize the DLA-DR antigen on the surface of canine leukaemias and lymphomas.

- We have also developed a method of conjugating these antibodies with methotrexate, one of the cytostatics used, inter alia, in acute lymphoblastic leukaemia – explains prof. Miążek, and prof. Rapak adds: - The obtained conjugates induced a high level of apoptosis against the canine leukaemia and lymphoma cell lines, so, to put it simply, they effectively killed cancer cells.

In a mouse model with transplanted canine lymphoma cells, complete remission was achieved after two weeks of administering a small dose of the antibody conjugate. The next step in the project is the implementation of the innovative drug. In human medicine, monoclonal antibodies have revolutionized the treatment of lymphomas. Scientists from Wrocław want to bring about such a revolution in the treatment of dogs.

– We have a prototype of a biological drug, the first in Poland and the second in the world. As part of the project, we are developing its production on a semi-technical scale with a view to eventually finding a company that will develop mass production so that the drug may be available on the market. Then we will be able to conduct tests on the target species, i.e. dogs, and not rodents, as we have done so far, says Prof. Miążek.

The scientists admit that a research unit or a small biotechnology company would not be able to bear the financial burden of such a venture. The funds required to produce a pharmaceutical-grade test sample will run into millions of dollars.

- The prevalence of leukaemias and lymphomas in humans and dogs is very similar and, moreover, they are spontaneous, which suggests that the environment they share is a risk factor. Lifestyle, exposure to carcinogenic factors from polluted air, highly processed food or plant protection products – all these components affecting the body for a long time, can trigger the disease – explains prof. Arkadiusz Miążek.

Prof. Andrzej Rapak emphasizes, however, that in the case of research carried out jointly with scientists from the UPWr, it is vital to use the achievements of human medicine and implement them in veterinary medicine.

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