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- Title
Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor-modified T-cell infusions for liver metastases.
- Authors
Saied, A; Licata, L; Burga, R A; Thorn, M; McCormack, E; Stainken, B F; Assanah, E O; Khare, P D; Davies, R; Espat, N J; Junghans, R P; Katz, S C
- Abstract
Our phase I Hepatic Immunotherapy for Metastases (HITM) trial tested the safety of chimeric antigen receptor-modified T-cell (CAR-T) hepatic artery infusions (HAI) for unresectable carcinoembryonic antigen (CEA)+ liver metastases (LM). High neutrophil:lymphocyte ratios (NLR) predict poor outcome in cancer patients and we hypothesized that NLR changes would correlate with early responses to CAR-T HAI. Six patients completed the protocol. Three patients received CAR-T HAI in dose escalation (1 × 108, 1 × 109 and 1 × 1010 cells) and the remainder received three doses (1 × 1010 cells) with interleukin (IL)2 support. Serum cytokines and NLR were measured at multiple time points. The mean NLR for all patients was 13.9 (range 4.8-38.1). NLR increased in four patients following treatment with a mean fold change of 1.9. Serum IL6 levels and NLR fold changes demonstrated a trend towards a positive correlation (r=0.77, P=0.10). Patients with poor CEA responses were significantly more likely to have higher NLR level increases (P=0.048). Increased NLR levels were associated with poor responses following CAR-T HAI. NLR variations and associated cytokine changes may be useful surrogates of response to CAR-T HAI.
- Subjects
LIVER cancer; IMMUNOTHERAPY; NEUTROPHILS; LYMPHOCYTES; CYTOKINES; HEPATIC artery; ANTIGEN receptors; CHIMERIC proteins
- Publication
Cancer Gene Therapy, 2014, Vol 21, Issue 11, p457
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/cgt.2014.50