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

Published

Journal Article

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 < 0.05) while IL-6 and IL-10 were elevated among those with progressive disease (p < 0.05). Peripheral blood CD8+/CD28+ T cells increased (p = 0.002), while the CD4+/CD25+/CD127+Treg cells decreased after therapy (p = 0.012). TCR diversity was substantially increased among the clinical responders.Conclusions: Combining HT with ACT plus either CT or anti-PD-1 antibody was safe, generated clinical responses in previously treated advanced cancers, and promoted TCR repertoire diversity and favorable changes in serum IL-2, IL-4, TNF-α, and IFN-γ levels in clinical responders.

Full Text

Duke Authors

Cited Authors

  • Qiao, G; Wang, X; Zhou, X; Morse, MA; Wu, J; Wang, S; Song, Y; Jiang, N; Zhao, Y; Zhou, L; Zhao, J; Di, Y; Zhu, L; Hobeika, A; Ren, J; Lyerly, HK

Published Date

  • November 2019

Published In

Volume / Issue

  • 36 / sup1

Start / End Page

  • 74 - 82

PubMed ID

  • 31795830

Pubmed Central ID

  • 31795830

Electronic International Standard Serial Number (EISSN)

  • 1464-5157

Digital Object Identifier (DOI)

  • 10.1080/02656736.2019.1647350

Language

  • eng

Conference Location

  • England