Adoptive cell transfer (ACT) therapy is used to treat patients with metastatic solid tumors. ACT involves the removal of some of the patient's cancer cells, and some of their immune T cells. When the cells are mixed together, specific parts of the cancer cells that stimulate the T cells to cause an immune attack can be identified. The T cells get expanded and re-infused into the patient to mount an immunological, anti-cancer response against the tumors. One of the challenges faced is selecting the appropriate T cells with proper antigen specificity.
In a new study appearing in the June 1 print issue of The Journal of Clinical Investigation, Nicholas Restifo and colleagues identified which cells are optimal for treating large, vascularized, established tumors. The authors use a mouse model that mimics the human clinical situation. They find that phenotypic and functional qualities of T cells are associated with the ability of ACT to cause regression of large, established melanomas. Seemingly paradoxical, naïve and early effector T cells are more effective for tumor treatment than more differentiated T cells.
In an accompanying commentary, Daniel Speiser and Pedro Romero write, "optimal therapeutic efficacy may depend on different T cell selection and preparation strategies" and these findings indicate that a pragmatic strategy for ACT is to keep the in vitro T cell expansion phase as short as possible to keep them naïve. These findings are important for development of improved adoptive immunotherapy approaches for treating tumors and established infectious diseases.
TITLE: Acquisition of full effector function in vitro paradoxically impairs the in vivo anti-tumor efficacy of adoptively transferred CD8+ T cells
AUTHOR CONTACT: Nicholas P. Restifo NIH - National Cancer Institute, Bethesda, MD USA Phone: 301 496-4904; Fax: 301 496-0011; E-mail: restifo@nih.gov.
View the PDF of this article at: https://www.the-jci.org/article.php?id=24480.
ACCOMPANYING COMMENTARY:
TITLE: Towards improved immunocompetence of adoptively transferred CD8+ T cells
AUTHOR CONTACT: Pedro Romero Ludwig Institute for Cancer Research, Lausanne, Switzerland Phone: 4121-314-0198; Fax: 41-21-314-7477; E-mail: pedro.romero@isrec.unil.ch.
View the PDF of this article at: https://www.the-jci.org/article.php?id=25427.
Journal
Journal of Clinical Investigation