Immune correlates of clinical benefit in a phase I study of hyperthermia with adoptive T cell immunotherapy in patients with solid tumors

Purpose: To characterize the T cell receptor (TCR) repertoire, serum cytokine levels, peripheral blood T lymphocyte populations, safety, and clinical efficacy of hyperthermia (HT) combined with autologous adoptive cell therapy (ACT) and either salvage chemotherapy (CT) or anti-PD-1 antibody in patie...

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Published in:International journal of hyperthermia 2019-11, Vol.36 (sup1), p.74-82
Main Authors: Qiao, Guoliang, Wang, Xiaoli, Zhou, Xinna, Morse, Michael A., Wu, Jiangping, Wang, Shuo, Song, Yuguang, Jiang, Ni, Zhao, Yanjie, Zhou, Lei, Zhao, Jing, Di, Yan, Zhu, Lihong, Hobeika, Amy, Ren, Jun, Lyerly, Herbert Kim
Format: Article
Language:English
Subjects:
Adolescent
adoptive cell therapy
Adult
Aged
Humans
Hyperthermia
Hyperthermia, Induced - methods
Immunotherapy, Adoptive - methods
Middle Aged
Neoplasms - therapy
ovarian cancer
pancreatic cancer
safety
T cell receptor repertoire
Young Adult
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Summary:Purpose: To characterize the T cell receptor (TCR) repertoire, serum cytokine levels, peripheral blood T lymphocyte populations, safety, and clinical efficacy of hyperthermia (HT) combined with autologous adoptive cell therapy (ACT) and either salvage chemotherapy (CT) or anti-PD-1 antibody in patients with previously treated advanced solid tumors. Materials and methods: Thirty-three (33) patients with ovarian, pancreatic, gastric, colorectal, cervical, or endometrial cancer were recruited into the following therapeutic groups: HT + ACT (n = 10), HT + ACT + anti-PD-1 inhibitor (pembrolizumab) (n = 11) and HT + ACT + CT (n = 12). Peripheral blood was collected to analyze TCR repertoire, measurements of cytokines levels and lymphocyte sub-populations before and after treatment. Results: The objective response rate (ORR) was 30% (10/33), including three complete responses (CR) (9.1%) and seven partial responses (PR) (21.2%) and a disease control rate (DCR = CR + PR + SD) of 66.7% (22 of 33). The most common adverse reactions, blistering, subcutaneous fat induration, local heat-related pain, vomiting and sinus tachycardia, were observed in association with HT. IL-2, IL-4, TNF-α, and IFN-γ levels in peripheral blood were significantly increased among the clinical responders (p 
ISSN:0265-6736
1464-5157
DOI:10.1080/02656736.2019.1647350