Editing of Endogenous Genes in Cellular Immunotherapies

Curr Hematol Malig Rep. 2020 Aug;15(4):235-240. doi: 10.1007/s11899-020-00587-0.

Abstract

Purpose of review: T cell-based cellular and antibody immunotherapies have dramatically altered the landscape of cancer treatment over the past decade. Over the same time span, gene editing technologies have enabled unprecedented degrees of genetic control.

Recent findings: Knock-outs of endogenous genes, especially based on electroporation of targetable nucleases such as CRISPR/Cas9, have rapidly proliferated. Simultaneous introduction of large DNA sequences can integrate new synthetic genetic instructions with specific endogenous loci to alter T cell function and specificity. Recently developed discovery technologies to perform genome-wide knock-out and large-scale knock-in screens in T cells can rapidly identify endogenous gene targets and therapeutic knock-in programs. Endogenous gene knock-outs and targeted knock-ins may offer the chance to expand beyond the current limitations of randomly integrating viral vector-based T cell therapies, and extend immunotherapies' therapeutic advances to wider hematologic and solid tumor indications.

Keywords: Cell therapy; Endogenous editing; Gene editing; Knock-ins; Knock-outs; Pooled screens.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Gene Editing*
  • Gene Expression Regulation, Neoplastic*
  • Gene Targeting*
  • Genetic Therapy* / adverse effects
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Prognosis
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents, Immunological