02 February 2022

Lymphocyte upgrade

Immunotherapy is a promising method of treating oncological diseases. T cells are endowed with a chimeric antigenic receptor (CAR), which allows them to recognize a certain protein on tumor cells and attach to it.

Immunotherapy has been quite successful against some types of cancer, but it has its drawbacks. The main ones are the depletion of T cells, non–recognition of the antigen and a complex treatment procedure that takes longer than some terminally ill patients can afford.

To solve these problems, an international team of researchers has developed genetically modified T-lymphocytes with a double receptor, which exhibit antitumor properties with constant unlimited functionality in vivo. Instead of conventional cytotoxic T-lymphocytes, scientists used rejuvenated T-cells created using induced pluripotent stem cell technology to produce CAR T-cells. Rejuvenated lymphocytes survive after being injected into the body much longer than conventional cytotoxic T-lymphocytes.

The researchers injected a chimeric antigen receptor that recognizes latent membrane protein 1 (LMP1) on the surface of cancer cells into induced pluripotent stem cells derived from LMP2-specific cytotoxic T lymphocytes. As a result, rejuvenated T cells with a dual receptor (dual receptor rejuvenated T-cells, DRrejT) were obtained, which recognize and are active against both LMP1 and LMP2.


When administered to mice that were injected with lymphomas associated with Epstein-Barr virus, DRrejT led to an increase in animal survival. They successfully suppressed not only the primary tumor, but also the re-introduced cancer cells, proving that they have unlimited availability and can remain active in vivo for a long time.

The researchers also created another type of DRrejT targeting CD19 and LMP2 antigens, which also demonstrated a strong tumor suppression effect.

The fight between the body's immune system and the tumor goes on continuously. As cancer cells mutate and metastasize, immune cells must continue to fight them. This continuous exposure often leads to depletion of CAR T cells, their antitumor effects weaken, and antigens are not recognized, which leads to cancer recurrence. The development of DRrejT gives new hope for cancer immunotherapy. Rejuvenated cells do not "get tired" longer and retain antitumor effect. In addition, if it is possible to develop DRrejTs that can avoid attacks from the patient's immune cells, a "ready-made" therapy for various types of cancer will be created. This means that the waiting time for patients will be significantly reduced.

Article S.Harada et al. Dual-antigen targeted iPSC-derived chimeric antigen receptor-T cell therapy for refractory lymphoma is published in the journal Molecular Therapy.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Juntendo University: Genetically Engineered Dual Receptor T-cells: Double Trouble for Cancer Cells.

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