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Gene editing of key transcription factors to improve the antitumor efficacy of Adoptive T cell Therapy

18th national competition for scientific and technical research

Immunotherapy and cancer

Senior Researcher : Juan José Lasarte Sagastibelza


The aim of this project was to introduce genetic modifications into T lymphocytes to give them a greater proliferative and antitumor capacity even in a hostile environment such as that found in tumors. The reprogramming of these lymphocytes, modulating the expression of different transcription factors that can modulate the state and activity of the lymphocytes, can improve their antitumor efficacy. We have found that the introduction of a gene encoding the EGF factor receptor, widely expressed in various types of tumors, increases the proliferative and antitumor capacity of T lymphocytes in adoptive transfer strategies.

Using CrisprCas9 technology, we have edited the Foxp3 gene [Foxp3down (dn)] in CD8 T lymphocytes and we have observed that such silencing worsens the antitumor response of CD8 T cells in adoptive cell transfer (ACT). In contrast, Foxp3 overexpression increases the antitumor efficacy of CD8 T lymphocytes. We have performed transcriptomic analysis of CD8 cells with silenced Foxp3 and with overexpressed Foxp3. Our data indicate that Foxp3 overexpression would favor differentiation towards memory cells and, on the contrary, Foxp3 editing would promote differentiation to effector cells. In the context of ACT, numerous studies indicate that memory T cells have a greater antitumor efficacy than effector cells. This would explain the behavior of the CD8 Foxp3UP and Foxp3dn T lymphocytes in antitumor efficacy experiments. Our data reveal a previously unknown role for Foxp3 in the regulation of CD8 T cell differentiation.


Scientific Production
Magazine Articles 4
Communications at national conferences 2
Communications at international conferences 3


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