Symptoms and General Pathology

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Cyclophosphamide

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Fludarabine phosphate

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Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Analgesics, Non-Narcotic

Peripheral blood lymphocytes will be collected and neoantigen reactive T cells(NRTs) will be generated in the laboratory;Both Fludarabine 30mg/m2/D and Cyclophosphamide 300mg/m2/D will be i.v. for 3 days before cell infusion; NRTs 0.5\~1 x 10\^10, will be i.v.Q3 weeks for total 4 doses;programmed cell death-1（PD1） inhibitor SHR-1210,200mg,will be i.v. Q3 weeks for total 4 doses,2 day2 prior to each NRTs infusion;Interleukin-2 (IL-2) will be continuous intravenous infused since the first day of the cell infusion for 5 consecutive days, 4000,000 international unit per day.All Patients will receive a total of 4 cycles of treatment.

Neoantigen Reactive T Cells in an expected volume of 100 milliliter（mL） will be given by intravenous injection over 2-10 minutes through either a peripheral or a central line.

Neoantigen Reactive T Cells(NRTs)

SHR-1210 200mg will be administered as an intravenous infusion over 60 minutes.

SHR-1210

Fludarabine(FLU) 30mg/m2/d×3d，3 days prior to each NRTs infusion as preconditional chemotherapy.

Cyclophosphamide(CTX) 300mg/m2/d×3d，3 days prior to each NRTs infusion as preconditional chemotherapy.

Interleukin-2(IL-2)will be continuous intravenous infused since the first day of the cell infusion for 5 consecutive days, 4000,000 international unit per day.

Baorui Liu, M.D & Ph.D

Zhengyun Zou, M.D & Ph.D

Baorui Liu, M.D. & Ph.D

Zhengyun Zou, M.D. & Ph.D

The purpose of this study is to see the safety and efficient of neoantigen reactive T cells (NRTs) combined with programmed cell death-1(PD-1) inhibitor（SHR-1210）in the treatment of Chinese patients with advanced refractory solid tumors.

The tumor-specific "none-self" immunogenic neoantigens encoded by either viral genes or somatic mutation genes, possess the potential to induce specific anti-cancer immunity, including cellular and humoral immune responses. Today, numerous clinical trials demonstrate that although these "none-self" antigens initiate the antigen-specific immunoglobulin G antibodies and cluster of differentiation 4（CD4）+/cluster of differentiation 8（CD8）+T-cells response, not all of them show a clinical benefit in the response rate, progression-free survival or overall survival.Immune tolerance induced by PD-1 or programmed cell death-ligand1（ PD-L1）maybe play a vital role for these negative outcomes.Personalized cell therapy plus checkpoint inhibitors maybe own a breakthrough in the treatment of those malignant diseases without standard options.Our center has successfully established a new method for preparing personalized neoantigen reactive T cells(NRTS) for adoptive cell therapy(ACT). Today, we will carry out a single center single arm clinical prospective study of NRTs combined with PD-1 inhibitor(SHR-1210) for the treatment of Chinese patients with advanced refractory solid tumors. Participants are assigned to receive 4 circles of cell therapy,and prior to each cycle's immunocytes treatment,preconditional chemotherapy and SHR-1210 will be carried out, and IL-2 continuous intravenous infusion（CIV） will also be given for 5 consecutive days after each time's cell infusion. The safety and clinical response rate（RR） are evaluated. Biomarkers and immunological markers are also monitored.

Neoantigen Reactive T Cells Combined With SHR-1210 for Chinese Patients With Advanced Refractory Solid Tumors

Single Center Single Arm Clinical Prospective Study of Neoantigen Reactive T Cells (NRTs) Combined With Programmed Cell Death-1（PD-1） Inhibitor in the Treatment of Chinese Patients With Advanced Refractory Solid Tumors

the duration is measured from the time of treatment to the time of death

T cells in the peripheral blood stimulated by tumor antigens for 24 hr，and then Interferon-gama secretion is measured

cytokines are measured by flow cytometry(FCM)

using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients

Response Rate（RR） will be evaluated according Response Evaluation Criteria in Solid Tumors

the duration of progression free survival is measured from the time of treatment to the first date that recurrent or progressive disease or for any reason of death is objectively documented.

Spots Global Cancer Trial Database for adoptive cell therapy(act)