Lentivirus Manufacturing Process for Primary T‐Cell Biofactory Production

Abstract

A process for maximizing the titer of lentivirus particles, deemed to be a necessity for transducing primary cells, is developed. Lentivirus particles, with a set of transgenes encoding an artificial cell‐signaling pathway, are used to transform primary T cells as vectors for calibrated synthesis of desired proteins in situ, that is, T‐cell biofactory cells. The process is also used to generate primary T cells expressing antigen‐specific chimeric antigen receptors, that is, CAR T cells. The two differently engineered primary T cells are expanded and validated for their respective functions, that is, calibrated synthesis of desired proteins upon engaging the target cells, which is specific for the T‐cell biofactory cells, and cytolysis of the target cells common to both types of cells. The process is compliant with current Good Manufacturing Practices and can be used to support the scale‐up for clinical translation.

Document Details

Document Type
Pub Defense Publication
Publication Date
May 10, 2020
Source ID
10.1002/adbi.201900288

Entities

People

  • Harikrishnan Radhakrishnan
  • Harold S Javitz
  • Parijat Bhatnagar

Organizations

  • Defense Advanced Research Projects Agency
  • National Cancer Institute
  • National Institute of Biomedical Imaging and Bioengineering
  • SRI International

Tags

Fields of Study

  • Biology

Readers

  • Computational Modeling and Simulation
  • Immunology
  • Oncology (Cancer Research).