Generating Antigen Presenting Cells by Direct Cellular Reprogramming

  • Ferreira Pires, Cristiana C. (PI)
  • Filipe Ribeiro Lemos Pereira, Carlos C. (CoPI)
  • Cristina Domingues Pedreiro, Susana S. (CoPI)
  • E Sousa, Caetano Reis C.R. (CoPI)
  • Papatsenko, Dmitri A. (CoPI)
  • Alves, Rita Alexandra Silvério R.A.S. (CoPI)
  • Granucci, Francesca F. (CoPI)
  • Shaiv, Kritika K. (CoPI)
  • Nascimento Caiado, Inês I. (CoPI)
  • Da Silva, Catarina Milheiro Soares C.M.S. (CoPI)

Project Details

Description

Cancer immunotherapy employs the cellular components of a persons' immune system to fight cancer. These new therapies, which include cancer vaccines, have being extensively studied by the medical and scientific community in recent years. Some of them rely on Dendritic Cells DCs, specialized in the recognition, processing and presentation of foreign antigens to the effector cells of the immune system. DC-based strategies have been studied to induce the patient immune system against residual cancer cells after chemotherapy. Usually DC-precursors are obtained from each patient and cultured in vitro before re-administration. However, limited number or immature cells are obtained using these approaches. Additionally, DC-precursors are already compromised in some cancer patients. Direct cellular reprogramming strategies offer exciting alternatives to overcome these limitations: the identity of a cell can be modified into another cell-type using lineage transcription factors, that bind DNA and activate or repress gene expression. Reprogramming from unrelated cell-types, not affected by cancer, would be a therapeutically attractive source of DCs. We will identify key transcription factors required to convert skin fibroblasts, easily isolated from the patient skin, into DCs. Reprogrammed DCs will be extensively characterized in order to confer their similarity with "natural" DCs. Their ability to efficiently present antigens to effector cells and to mount an attack against cancer cells will be tested. Ultimately, this project will represent a pioneering contribution for applying direct reprogramming for inducing immunity and generating novel DC-based immunotherapies for cancer.

StatusFinished
Effective start/end date1/06/1831/12/21

Funding

  • Fundação para a Ciência e a Tecnologia: $281,801.00

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