Natural killer T (NKT) cells are a unique subset of lymphocytes that present a mixed T-NK phenotype. Our hypothesis is that Natural killer T cells may decrease the tumor burden and improve overall survival. The purpose of this study is to determine whether Natural killer T (NKT) cells are effective and safe in the treatment of patients with unresectable advanced solid tumor.
According to the Annual Report of Cancer Registration in China 2014, lung cancer, gastric cancer, liver cancer and colorectal cancer have become the top 4 solid tumors with the highest morbidity and mortality rates. So far, the main treatment modalities for these tumors have been surgery, radiotherapy and chemotherapy. However, the effect of conventional therapy on advanced cancer is limited, tumor metastasis is the major cause of death in patients with advanced cancer. With the development of oncology and immunology in recent years, immunotherapy represents a novel path to obtain a durable and long-lasting response in cancer patients. Natural killer T (NKT) cells are a unique subset of lymphocytes that present a mixed T-NK phenotype. NKT cells are expanded conventionally from peripheral blood mononuclear cells by addition of a variety of cytokines in vitro culture. Our previous studies demonstrated that the expansion of NKT cells in a clinical usage scale from peripheral blood mononuclear cells is feasible. Those expanded NKT cells exhibit antitumor effect in vitro and in vivo (tumor -bearing nude mice) against a variety of tumor cells. Furthermore, intravenous infusion of a single dose of 4X10\^9 NKT cells in mice has been proved safe. The purpose of this study is to evaluate the efficacy and safety of NKT cells in patients with unresectable advanced solid tumor.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
120
The eligible patients are infused with two doses of (4±0.5)x10\^9 NKT cells in one course of treatment.
Hua Xin Hosptial First Hosptial of Tsinghua University
Beijing, China
RECRUITINGShanghai Public Health Clinical Center
Shanghai, China
RECRUITINGThe incidence of adverse events following infusion of NKT cells
liver dysfunction, kidney dysfunciton, shivering, diarrhea, fever and more
Time frame: 30 days post-infusion
Objective Response Rate (ORR), confirmed by CT or MRI, or confirmed by biopsy
The proportion of participants with complete remission and partial remission which judged by RECIST v1.1
Time frame: up to 24 weeks
Hematology
Hematology, include erythrocytes, leukocytes, platelets, T lymphocytes, B lymphocytes, Natural killer cell, NKT, CD4/CD8, Th1/Th2, Th17 cell and Treg lymphocytes
Time frame: Baseline, 1 day, 7 days, 14 days and 28 days after cell infusion
Serological analysis
Serological analysis, include immunoglobulin G, immunoglobulin A, immunoglobulin D, immunoglobulin E and immunoglobulin M. Albumin (ALB), Alanine aminotransferase (ALT), Aspartate Aminotransferase (AST), Prealbumin (PA), total bilirubin (TB), and direct bilirubin (DB); Blood urea nitrogen (BUN), Urea (UA), and Crea (Cr); Total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), very low density lipoprotein cholesterol (VLDL-C), and Non-HDL-C; blood sugar
Time frame: Baseline, 1day, 7 days, 14 days and 28 days after cell infusion
Overall Survival (OS)
The time from the beginning of ransomization to death from any cause
Time frame: Approximately 3 years
Progression-Free Survival (PFS)
The time from randomization to the first recording of disease progression (RECIST v1.1)
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Time frame: Approximately 1 years
Tumor Marker
CEA, AFP and more
Time frame: up to 24 weeks