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CAR-T 123 production in K562 red cell leukemia cells for therapeutic use in patients with acute myeloid leukemia

Grant number: 17/16319-7
Support Opportunities:Research Grants - Innovative Research in Small Business - PIPE
Duration: October 01, 2018 - June 30, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Patricia Bortman Rozenchan
Grantee:Patricia Bortman Rozenchan
Host Company:Celluris Participações Ltda
CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
Atividades de serviços de complementação diagnóstica e terapêutica
City: São Paulo
Associated researchers:Bryan Eric Strauss ; Luciane Bleivas Elmalem
Associated grant(s):21/03578-0 - Chimeric anti-mesothelin receptor in tandem with the interleukin receptor (CAR-T anti-MSLN/ILR2) production in t lymphocytes for therapeutic use in patients with positive mesothelin expression tumors, AP.PIPE

Abstract

One of the great challenges of cancer treatments is that at some point the tumor cells may no longer respond to the treatment, or after a certain time free of the disease, the patient may present a recurrence. Thus, there is a great demand for new methods in the treatment of cancer, since the conventional methods of treatment; surgery, radiation and chemotherapy, do not guarantee cure for all patients. Celluris works in the immunotherapy area, using CarT technology. This solution is being considered a paradigm shift in cancer treatment since it enables the patient's own cells to fight tumor cells. Our goal in the present proposal is to produce chimeric receptor for CD123 and to test its functionality for later use in patients with acute myeloid leukemia. To this end, we will produce lentivirus containing the CD123 expression cassette in HEK293T cells, then transduce that vector into K562 cells and verify the functionality of our CAR-T by binding to the specific antigen bound to a fluorochrome. There are almost 200 clinical trials around the world with this technology, and the results have been very promising, with success rates in some cases above 80% for patients who were no longer responding to chemotherapy or who relapsed after bone marrow transplantation. The FDA has recently approved the use of CART by Novartis and Kite is expecting to be approved in the coming. Here in Brazil, Anvisa has already made a public call, where showed a favorable positioning regarding the approval of this technology. With the results obtained in the present proposal, that is, the standardization of CAR-T production and the verification of its in vitro functionality, we intend to initiate a translational protocol, where we will test our CAR-T 123 in cells obtained from patients with acute myeloid leukemia. This step will be fundamental so that we can establish a Brazilian clinical trial, a determining factor for this state-of-the-art technology to be implemented in our country, we will generate a critical mass of results obtained in Brazil, so that the technology can be submitted for Anvisa's approval. Thus, in addition to technological development, we will gain independence in this therapeutic approach. We established two very important partnerships, namely Dr. Bryan E. Strauss of Icesp, where we will do the lenti-viral production, with all the required NB2 structure and also with the Hospital Israelita Albert Einstein, where we will make use of the clean room structure of the onco-hematology department, led by Dr. Nelson Hamerschlak. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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