Combination of Cytokine-Induced Killer Cells and Programmed Cell Death-1 Blockade Works Synergistically to Enhance Therapeutic Efficacy in Metastatic Renal Cell Carcinoma and Non-Small Cell Lung Cancer

Frontiers in Immunology
Zibing WangQuanli Gao

Abstract

Programmed cell death-1 (PD-1) inhibition therapy has changed the treatment paradigm of metastatic renal cell carcinoma (MRCC) and non-small cell lung cancer (NSCLC). However, attempts to use the drug as a single agent have achieved only limited clinical success. To further enhance the clinical benefits of monotherapy, combination therapies will likely be necessary. Cytokine-induced killer (CIK) cells are a heterogeneous subset of ex vivo expanded T lymphocytes that have been shown to prolong the survival of cancer patients. We are conducting a study to evaluate the efficacy of PD-1 inhibitor in combination with CIK cells in relapsed/refractory MRCC and NSCLC and to analyze potential biomarkers to predict which patients will benefit most from the combined therapy. The results of two patients treated in an ongoing clinical trial for MRCC and NSCLC are described here. The tumor biopsy from Patient 1 exhibited moderate CD3+ T cell infiltration, but no PD-1 or PD-L1 expression. The tumor cells from Patient 2 strongly expressed PD-L1, and there was extensive tumor infiltration by CD3+ T cells; however, no PD-1 staining was seen. Non-synonymous single nucleotide variant (nsSNVs), along with higher indel mutations, in Patient 1 and ns...Continue Reading

References

May 15, 2012·Cancer Immunology, Immunotherapy : CII·Runmei LiHui Li
Nov 30, 2012·Clinical & Developmental Immunology·Clara E JäkelIngo G H Schmidt-Wolf
Jul 25, 2015·Nature Reviews. Cancer·Ignacio MeleroJohn Haanen
Jan 21, 2016·Cancer Immunology Research·Antoni RibasBegoña Comin-Anduix
Jul 20, 2016·Journal of Immunology Research·Lu HanQuan-Li Gao
Jun 28, 2017·Nature Reviews. Clinical Oncology·Mizuki NishinoF Stephen Hodi

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Methods Mentioned

BETA
biopsy
biopsies
exome sequencing

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