Tumor lysate or carcinoembryonic antigen (CEA) derived DCs-based therapy is safe and can elicites remarkable T-cell responses but mostly did not really transfer into significant clinical benefit. One possible reason is the lack of effective antigen and the immunosuppressive microenvironment. Now we are exploring another new strategy, prediction of neoantigen for priming DCs as cell-based therapy with or without booster of anti-VEGF/anti-PD-1.
The human immune system can recognize and destroy cancer cells but cancer cells are capable of escaping from immune system by different ways, including the PD-1/PDL-1 axis and the VEGF signaling pathway. The PD-1/PD-L1 axis represents an adaptive immune resistance mechanism exerted by tumor cells. Previous study also revealed VEGF-A could induce tumor-associated macrophages, Treg cells, and myeloid-derived suppressor cells, creating an immunosuppressive microenvironment that prevent the maturation of dendritic cells (DCs) and inhibit the activation of NK cells and T cells. Our research group already completed some early phase clinical trials of DCs-based therapy, which illustrated tumor lysate or carcinoembryonic antigen (CEA) derived DCs-based therapy is feasible and safe in patients with advanced colorectal cancer and lung cancer, respectively. However, although DCs-based therapy elicited remarkable T-cell responses but mostly did not really transfer into significant clinical benefit in previous study. One possible reason is the lack of effective antigen and the immunosuppressive microenvironment. Now we are exploring another new strategy, prediction of neoantigen for priming DCs as cell-based therapy with or without booster of anti-VEGF/anti-PD-1.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Approximately 1.5 x 10\^6±20% cells will be subcutaneously injected to the patient's inguinal area (either left side or right side can be injected, only one area will be injected each time) on day 1, 8, 15, 29, 85, 141, 197, 253 and 309.
Lenvatinib 10mg/day on day 43-77
Nivolumab 3mg/kg on day 43, 57 and 71.
Kaohsiung Medical University Hospital
Kaohsiung City, Taiwan
NOT_YET_RECRUITINGNational Cheng-Kung University Hospital
Tainan, Taiwan
RECRUITINGNational Institute of Cancer Research
Tainan, Taiwan
RECRUITINGNumber of subjects experienced limiting toxicities in the first 6 weeks.
The following toxicities that happened during first 6 weeks are considered LTs. Toxicities are graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0: * \>=Grade 3 non-hematological toxicity * \>=Grade 4 hematological toxicity * Any death not clearly due to the underlying disease or extraneous causes. * Any case meeting Hy's law * Recurrent grade 2 pneumonitis
Time frame: 6 weeks
Percentage of patients who had a clinical response
Response was assessed by the iRECIST.
Time frame: 1 year
Number of participants who did not progressed or survived at 1 year
1 year progression-free survival and overall survival rate
Time frame: 1 year
Number of subjects experienced any ≥ grade 3 toxicities.
any ≥ grade 3 toxicities rate
Time frame: 1 year
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