00085472can142277-sup-135754_1_supp_2687506_ncvw2k.pptx (122.69 kB)

Supplemental Figure S3 from Akt Inhibition Enhances Expansion of Potent Tumor-Specific Lymphocytes with Memory Cell Characteristics

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posted on 2023-03-30, 23:31 authored by Joseph G. Crompton, Madhusudhanan Sukumar, Rahul Roychoudhuri, David Clever, Alena Gros, Robert L. Eil, Eric Tran, Ken-ichi Hanada, Zhiya Yu, Douglas C. Palmer, Sid P. Kerkar, Ryan D. Michalek, Trevor Upham, Anthony Leonardi, Nicolas Acquavella, Ena Wang, Francesco M. Marincola, Luca Gattinoni, Pawel Muranski, Mark S. Sundrud, Christopher A. Klebanoff, Steven A. Rosenberg, Douglas T. Fearon, Nicholas P. Restifo

Supplemental Figure S3. Surface phenotype of Akti-treated and vehicle TIL isolated from patient with melanoma and expanded to clinical scale for 30 days prior to adoptive-transfer into humanized mouse model.

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ARTICLE ABSTRACT

Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) results in complete regression of advanced cancer in some patients, but the efficacy of this potentially curative therapy may be limited by poor persistence of TIL after adoptive transfer. Pharmacologic inhibition of the serine/threonine kinase Akt has recently been shown to promote immunologic memory in virus-specific murine models, but whether this approach enhances features of memory (e.g., long-term persistence) in TIL that are characteristically exhausted and senescent is not established. Here, we show that pharmacologic inhibition of Akt enables expansion of TIL with the transcriptional, metabolic, and functional properties characteristic of memory T cells. Consequently, Akt inhibition results in enhanced persistence of TIL after adoptive transfer into an immunodeficient animal model and augments antitumor immunity of CD8 T cells in a mouse model of cell-based immunotherapy. Pharmacologic inhibition of Akt represents a novel immunometabolomic approach to enhance the persistence of antitumor T cells and improve the efficacy of cell-based immunotherapy for metastatic cancer. Cancer Res; 75(2); 296–305. ©2014 AACR.