T-cell receptor gene transfer by lentiviral vectors in adoptive cell therapy

Abstract

Adoptive cell therapy can be envisioned as a promising strategy for tumour immunotherapy. However, existing protocols of adoptive cell therapy still require optimisation as many factors, such as specificity, avidity, level of differentiation and amount of transferred T lymphocytes, can influence their immunocompetence and in vivo functionality. In particular, the need to reduce the in vitro expansion phase and to obtain large numbers of tumour-reactive T cells, as a favourable condition for cancer regression, make TCR gene transfer a potentially ideal tool to overcome the limits of adoptive cell therapy strategies. Here, the authors review the state-of-the-art and recent advances in TCR transfer with particular emphasis on lentiviral vector systems. Initial data from preclinical models and recent clinical trials encourage optimisation of a safe, simplified and stable transfer system. In this regard, HIV-based vectors are emerging as good alternative candidates over the most widely used oncoretroviral vectors due to their peculiar molecular features that fit the ideal conditions for donor T cell in vitro manipulation.

Keywords::

• adoptive cell therapy
• cancer
• cytotoxic T lymphocytes
• lentiviral vectors
• transgenic TCR