Anti-Inflammatory Agents

All Drugs and Chemicals

Antineoplastic Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Nimotuzumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Peripheral blood lymphocytes will be collected. The NK cell will be selected and expanded ex vivo, then adaptive transfer back into patients. A total of 5.0 x 10\^8/L NK cells will be infused in one cycle.To avoid allergic reactions, 50 mg hydrocortisone was intramuscularly injected into patient 30 min before cells infusion every time. Best supportive care was also provided for patients. Nimotuzumab will be used 24 hours before infusion. Patients continued receiving treatment unless they had unacceptable adverse effects, or progressive disease confirmed by CT and PET-CT or they withdrew consent.

Nimotuzumab will enhance the ADCC effect of NK Cell adaptive transfer

NK Cell adaptive transfer

Shixiu Wu, Doctor

NK cells can persist and expand in vivo following adoptive transfer and may have a role in the treatment of late stage malignancies. NK also express an activating Fc receptor that mediates antibody-dependent cellular cytotoxicity (ADCC) and production of immune modulatory cytokines in response to antibody-coated targets. Nimotuzumab, an monoclonal antibody against EGFR (epidermal growth factor receptor), may enhance the ADCC effect of NK cell. This study will evaluate the safety of combination of nimotuzumab and NK Cell in treating advanced cancer patients. Blood samples will also be collected for research purposes.

This is a phase I clinical study of expanded NK cells from autologous origin. The NK cell will be selected and expanded ex vivo and infused back into patients. Nimotuzumab will be used 24 hours before infusion. 21 advanced cancer patients are planned to receive two cycles of NK cells and Nimotuzumab treatment. Biomarkers and immunological markers are collected and analyzed as well.

Immunotherapy of Advanced Cancer Using a Combination Nimotuzumab and NK Cells

A Phase I Trial of Combined Nimotuzumab With NK Cells Adoptive Transfer for the Treatment of Advanced Cancer

From date of randomization until the date of first documented progression or date of death from any cause

The time from randomization to death from any cause

Peripheral circuiting tumor DNA is collected at baseline and 6 weeks after last treatment

Number of Patients with Clinical or Biological Treatment-related Adverse Events and/or Dose Limiting Toxicities as a Measure of Safety and Tolerability of a Combination of Nimotuzumab and NK Cell as assessed by CTCAE v4.0

Response will be evaluated according to RECIST v1.1

Shanghai bokang bioengineering co., LTD

Hangzhou Cancer Hospital

President of Hangzhou Cancer Hospital

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Carcinoma, Renal Cell

Kidney Neoplasms

Carcinoma

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

RCC patients (30 pts) will include patients with kidney cancer (renal cell cancer).

Investigators will collect and analyze:

* blood sample,
* urine sample,
* kidney tissue sample (healthy tissue, carcinomatous tissue and borderline tissue between them).

In this group (30 patients) will be recruiting healthy patients (volunteer).

Investigators will collect and analyze:

* blood sample.

Dean Markić, MD, PhD

Renal cell cancer (RCC) is one of the most important urogenital tumors because of it's high mortality and increasing incidence. RCC, which accounts about 3% of all malignant tumors in the adults, is the most lethal urogenital cancer. The high mortality rate stimulate investigator groups to study RCC pathogenesis including immunological part. It is interesting that immunotherapy was firstly started in patients with metastatic RCC using IL-2 and interferon gamma. The first results were promising but the exact mechanism of acting was not found. In the RCC, as in the others tumors, immune cells (T lymphocytes, NK and NKT cells) are responsible for main antitumor effect. Their effect was caused by cytotoxic activity on the tumor cells. In the investigation investigators will determine patterns of aggregation of tumor infiltrating immune cells in the blood, healthy kidney and carcinomatous tissue. But, presence of this cells not implicated that this cells are active. Their activity will be determined by proofing cytotoxicity of different subgroup of immune cells. In that way investigators will present different patterns of aggregation of tumor infiltrating immune cells and their cytotoxicity which will direct that this cells are active with antitumor effect. Correlation of collected data with classical prognostic factors in the patients with RCC as tumor staging, tumor grading (Fuhrman) and histological subtype will help to determine some immunological factors as possible new prognostic factors. For conclusion, the results of this study will allow better understanding of RCC pathogenesis, specially their immunological part and become a foundation for the future investigations.

Cellular immunity will be investigated in the two group of patients: operated patients with RCC and healthy volunteers.

In the study investigators will determine patterns of aggregation of tumor infiltrating immune cells in the blood (RCC patients and volunteers), healthy kidney and carcinomatous tissue as their cytotoxicity (only RCC patients).

Investigators will determine:

1. presence of different immune cells in the blood and kidney tissue (T lymphocytes, NK cells, NKT cells, T regulatory cells),
2. presence and distribution of cytolytic molecule perforin and granulysin in immune cells (T lymphocytes, NK cells, NKT cells) in the blood, kidney tissue and urine
3. NK cytotoxicity
4. possible correlation between presence of immune cells and clinical prognostic factors

Investigators will collect:

1. patients with kidney cancer:

   * blood,
   * urine,
   * kidney tissue removed during operation (healthy kidney tissue, carcinomatous tissue and tissue form the border)
2. healthy control:

   * blood

Cellular Immunity and Renal Cell Cancer

NK Cells, Tumor Infiltrating Lymphocytes and Cell Cytotoxicity in Renal Cell Cancer - Observational Study

All included patients will signed informed consent. Individual participant data will not be shared with other researchers.

Determination of distribution of immune cells between two groups in their blood samples with their comparison.

Determination of distribution of immune cells between different tissue samples with their comparison

Clinical Hospital Center Rijeka

Prof. of Urology, MD, PhD, FEBU

Respiratory Tract (Lung and Bronchial) Diseases

Adenocarcinoma of Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Adenocarcinoma

The EGFR mutation positive patients were with the principles of randomized and NK cells treatment.

The EGFR mutation positive patients were with the principles of randomized and without NK cells treatment .

The EGFR mutation negative patients were with the principles of randomized and NK cells treatment .

The EGFR mutation negative patients were with the principles of randomized and without NK cells treatment.

NK cells were generated in good manufacturing practice (GMP) condition. In brief, PBMCs were isolated from 50mL patient's blood with Ficoll-Hypaque(Morecell Biomedical Co. Ltd., Shenzhen, China). Then the Human NK Cell Culture Kit (Cat. No.

MCF-004, Morecell Biomedical Co. Ltd., Shenzhen, China) and Serum-free Medium for NK Cells (MCM-002, Morecell Biomedical Co. Ltd., Shenzhen, China) was used for induction of NK cells according to the manufacturer's instructions. Three days before NK cell transfusion, the NK cells were sampled and sent to detect the NK cell quality.

NK cells

TAO LIU, PHD

Meiling Zhou, Master

This study was attempted to investigate the efficiency of NK cells immunotherapy on non-small cell lung cancer with and without EGFR mutation, and evaluated response rate (RR) and the progression-free survival (PFS).

Investigators will enrolle 100 patients who met the enrollment criteria. 50 patients were clinically confirmed EGFR mutation positive. They were divided into two groups (group A and group C according to if accepted NK therapy) in accordance with the principles of randomized. The rest 50 patients which were EGFR mutation negative were also divided into two groups (group B and group D) in accordance with the principles of randomized to be paired respectively with group A and group C. Comparison of lymphocyte number, serum tumor related biomarkers, circulating Tumor Cell (CTC), KPS and survival curves was carried out before after NK cell immunotherapy. The safety and short-term effects were evaluated followed by the median PDA, response rate assessment.

Effect of NK Cell Immunotherapy on Advanced Lung Adenocarcinoma Adenocarcinoma With EGFR Mutation

Effect of Autologous NK Cell Immunotherapy on Advanced Lung Adenocarcinoma With EGFR Mutation: a Preliminary Clinical Study

Investigators evaluated the Karnofsky Performance Status (KPS) according to the comprehensive assessment of clinical activity, disease level, and self-care ability.

Status (KPS) according to the comprehensive assessment of clinical activity, disease level, and self-care ability.

Based on the Response Evaluation Criteria Solid Tumors (RECIST), the therapeutic effect was divided into complete response (CR), partial response (PR),stable disease (SD), progressive disease (PD). Investigators calculated the sum area of all tumors 3 months after NK treatment. The recent curative effect must have been maintainedat \>4 weeks; CR + PR denoted the effective response rate (RR).

Patients were detected Lymphocyte subgroups of 1ml peripheral blood by Flow cytometer (BD FACSCalibur), which inclunde the T cell number, CD4T cell number, CD8 T cell number and NK cell number.

Patients were detected the Serum Carcinoembryonic antigen (CEA) and CA125 level by Elisa kit.Investigators compared the level of CEA and CA125 in serum before and 3 months after NK cell therapy to perform the therapeutic evaluation.

factor to identify patients tumor recurrence.We then compared the level of CEA and CA125 in serum before and 3 months after NK cell therapy to perform the therapeutic evaluation.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immunotherapy of Advanced Cancer Using a Combination Nimotuzumab and NK Cells	NCT03554889	Advanced Cancer ADCC NK Cell Mediate... Nimotuzumab Adaptive Transf...	NK Cell adaptiv... Nimotuzumab	18 Years - 75 Years	Hangzhou Cancer Hospital
Immunotherapy of Advanced Cancer Using a Combination Nimotuzumab and NK Cells	NCT03554889	Advanced Cancer ADCC NK Cell Mediate... Nimotuzumab Adaptive Transf...	NK Cell adaptiv... Nimotuzumab	18 Years - 75 Years	Hangzhou Cancer Hospital
Cellular Immunity and Renal Cell Cancer	NCT04377113	NK Cell Mediate... NK Cell Cytokin... Kidney Cancer		18 Years -	Clinical Hospital Center Rijeka
Effect of NK Cell Immunotherapy on Advanced Lung Adenocarcinoma Adenocarcinoma With EGFR Mutation	NCT03662477	NK Cell Mediate...	NK cells	35 Years - 75 Years	Shenzhen Fifth People's Hospital

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