Abstract 1687P
Background
Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has shown clinical responses in the treatment of metastatic melanoma. Improvement in the persistence of TILs is an area of ongoing investigation. Emerging data has demonstrated that levels of circulating metabolites significantly affect T cell function and survival in multiple pre-clinical models of ACT. However few studies have interrogated the circulating metabolome in patients undergoing ACT. We aimed to investigate changes in the serum metabolome in patients with metastatic melanoma undergoing ACT with TILs.
Methods
Samples were obtained longitudinally from 9 patients with metastatic cutaneous melanoma undergoing ACT with TILs. Sample A was obtained prior to lymphodepletion, sample B was collected after lymphodepletion one hour prior to TIL infusion, sample C was obtained 24 hours post TILs infusion and sample D was collected 4 weeks post infusion. Serum metabolites were measured using targeted mass spectrometry and differences in metabolites were compared using Random Forest, Multidimensional scaling analysis and the U-Mann-Whitney test.
Results
Comparison between samples A and B revealed a significant increase in only ortho-hydroxypheylacetic acid, however there was a significant decrease in multiple metabolites. Comparison of samples B to C showed significant decrease in multiple metabolites including Lysophosphatidyl choline (LPC) 16:0 and LPC 18:0. Comparison of sample C to D showed a significant decrease of ortho-hydroxyphenylacetic acid and increase in LPC 16:0 and LPC 18:0. In ex vivo experiments, human T cells pretreated with LPC 18:0 demonstrated increased proliferation and IL-2 production in a dose dependent manner.
Conclusions
ACT with TILs caused dynamic changes in circulating metabolites. Most significantly, there was a decrease in LPC after TILs infusion suggesting LPC uptake by the infused T cells. LPC has been shown to be involved in CD8+ memory T cell maintenance. Exposure to LPC pre-infusion may potentially improve infused CD8+ T cell IL-2 production and engraftment warranting further investigation.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Vilbert: Financial Interests, Institutional, Funding: Alamos Gold, Inc. T. Pimentel Muniz: Financial Interests, Institutional, Funding: Alamos Gold, Inc; Financial Interests, Personal, Research Grant: Novartis. E.C. Koch: Financial Interests, Personal, Invited Speaker: Novartis, MSD; Financial Interests, Personal, Advisory Board: Novartis, MSD; Financial Interests, Institutional, Other, Funding: Alamos Gold Inc.; Financial Interests, Institutional, Research Grant: Novartis. M.O. Butler: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, EMD Serono, GlaxoSmithKline, Immunocore, Merck, Novartis, Pfizer, Sanofi; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Other: Adaptimmune, GlaxoSmithKline. S. Saibil: Financial Interests, Personal, Advisory Board: Novartis, Janssen. All other authors have declared no conflicts of interest.