Antigen-specific T Cells Against Lung Cancer

Important Regulatory Notice:

This trial record is only for global academic information registration on ClinicalTrials.gov. Neither the sponsor Beijing Meikang Jimian Biotechnology Co., Ltd. nor collaborator Shenzhen Geno-Immune Medical Institute has obtained NMPA clinical trial approval or clinical technology filing permission to carry out interventional cell therapy trials in mainland China.

ClinicalTrials.gov registration alone does not represent legal approval by Chinese health and drug regulatory authorities.

Lung cancer is a malignancy characterized by uncontrolled cell growth in tissues of the lung. There are two main types of lung cancer, small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). In 2012, lung cancer occurred in 1.8 million people and resulted in 1.6 million deaths worldwide. Common treatments include surgery, chemotherapy, and radiotherapy, but in relapsed cancer patients, such treatments often have limited successes.

In this study, the participant's peripheral blood mononuclear cells will be collected for antigen-specific T cell preparation, and/or modified using an advanced lentiviral vector system. Then the antigen-specific T cells, called engineered immune effectors (EIEs) or chimeric antigen receptor modified-T cells (CAR T), which can recognize specific molecules that are expressed by the lung cancer cells, are given back to the participant by intravenous infusion.

The purpose of this clinical trial is to assess the feasibility, safety and efficacy of T cell immunotherapy targeting single or multiple cancer antigens. The lung cancer antigens include known tumor antigens such as MAGE-A1, MAGE-A4, MucI, GD2, and mesothelin, as well as novel cancer antigens. Another goal of the study is to learn more about the persistence and function of the specific CAR T cells in the body.

• Lung cancer-specific T cells (Biological): 1 infusion, for 1x10\^6\~1x10\^7 cells/kg via IV

Primary outcomes

• Safety of engineered T cells in patients using CTCAE version 4.0 standard to evaluate the level of adverse events [3 months]: Physiological parameter (measuring cytokine response)

Secondary outcomes

• Persistence and proliferation of engineered antigen-specific T cells in patients [3 months]: The expansion and functional persistence of ex vivo engineered T cells in the peripheral blood of patients will be examined on Day 7, 14, 21, 28, 60 and 90 after infusion.
• Anti-tumor effects [1 year]: Objective response, such as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Patients with stage III, IV or relapsed lung cancer confirmed by histology and biopsy.
2. Age: ≥ 18 years and ≤ 80 years.
3. 4 weeks at least since last chemotherapy or radiotherapy and 2 weeks at least since last systemic steroid hormone and other immunosuppressive therapy.
4. Side Effects of Chemotherapy have subsided.
5. Cancer specific antigens are identified and shown to express at high levels (>2+) in malignant tissues by immuno-histochemical staining or flow cytometry.
6. Karnofsky/Lansky ≥ 50%.
7. Expected survival ≥ 6 weeks.

Initial hematopoietic conditions with

* neutrophils (ANC) ≥ 1×10\^6/L;
* platelet (PLT) ≥ 1×10\^8/L.

Proper renal and hepatic functions (ULN denotes "upper limit of normal range") with

* serum creatinine ≤ 2×ULN;
* serum bilirubin ≤ 3×ULN;
* AST/ALT ≤ 5×ULN.

  10\. Oxygen saturation ≥ 90%. 11. Written, informed consent obtained prior to any study-specific procedures.

Exclusion Criteria:

1. Airway obstruction caused by tumor.
2. History of epilepsy or other central nervous system diseases.
3. Patients who require systemic corticosteroid or other immunosuppressive therapy.
4. History of prolonged or serious heart disease during QT.
5. history of serious cyclophosphamide toxicity.
6. Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug or previous participation in any immune cell therapy study.

Inadequate liver and renal function with

* serum creatinine > 2.5 mg/dl;
* serum (total) bilirubin > 2.0 mg/dl;
* AST \& ALT > 3 x ULN.

  8\. Pregnant or lactating females. 9. Serious active infection during screening. 10. Active HIV, Hepatitis B virus (HBV), Hepatitis C virus (HCV) infection or uncontrolled infection.

  11\. Patients, in the opinion of investigators, may not be eligible or not able to comply with the study.

• Lung-Ji Chang, PhD, Principal investigator, Shenzhen Geno-Immune Medical Institute