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Clin Cancer Res. 2019 Apr 1;25(7):2096-2108. doi: 10.1158/1078-0432.CCR-18-3496. Epub 2018 Dec 20.

A Pilot Trial of the Combination of Transgenic NY-ESO-1-reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab.

Author information

1
Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
2
Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California.
3
Department of Pathology, University of California Los Angeles, Los Angeles, California.
4
Department of General Internal Medicine and Health Services Research, University of California Los Angeles, Los Angeles, California.
5
Division of Molecular and Cellular Oncology, Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California.
6
Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California.
7
Division of Surgical-Oncology, Department of Surgery, University of California Los Angeles, Los Angeles, California.
8
Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California. asingh@mednet.ucla.edu aribas@mednet.ucla.edu.
9
Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, California.
10
Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California.

Abstract

PURPOSE:

Transgenic adoptive cell therapy (ACT) targeting the tumor antigen NY-ESO-1 can be effective for the treatment of sarcoma and melanoma. Preclinical models have shown that this therapy can be improved with the addition of dendritic cell (DC) vaccination and immune checkpoint blockade. We studied the safety, feasibility, and antitumor efficacy of transgenic ACT with DC vaccination, with and without CTLA-4 blockade with ipilimumab.

PATIENTS AND METHODS:

Freshly prepared autologous NY-ESO-1-specific T-cell receptor (TCR) transgenic lymphocytes were adoptively transferred together with NY-ESO-1 peptide-pulsed DC vaccination in HLA-A2.1-positive subjects alone (ESO, NCT02070406) or with ipilimumab (INY, NCT01697527) in patients with advanced sarcoma or melanoma.

RESULTS:

Six patients were enrolled in the ESO cohort, and four were enrolled in the INY cohort. Four out of six patients treated per ESO (66%), and two out of four patients treated per INY (50%) displayed evidence of tumor regression. Peripheral blood reconstitution with NY-ESO-1-specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. Tracking of transgenic T cells to the tumor sites was demonstrated in on-treatment biopsies via TCR sequencing. Multiparametric mass cytometry of transgenic cells demonstrated shifting of transgenic cells from memory phenotypes to more terminally differentiated effector phenotypes over time.

CONCLUSIONS:

ACT of fresh NY-ESO-1 transgenic T cells prepared via a short ex vivo protocol and given with DC vaccination, with or without ipilimumab, is feasible and results in transient antitumor activity, with no apparent clinical benefit of the addition of ipilimumab. Improvements are needed to maintain tumor responses.

PMID:
30573690
PMCID:
PMC6445780
[Available on 2020-04-01]
DOI:
10.1158/1078-0432.CCR-18-3496

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