Table 1 Completed and ongoing clinical trials

NCT03987867

[92]

Autologous CIK cells with PD-1 inhibitor (IBI308, sintilimab) and chemotherapy

Advanced NSCLC

n = 30

Objective response rate (ORR) was calculated by the percentage of patients with a confirmed complete (CR) or partial response (PR).

IBI308 intravenous infusion 200 mg d1; Pemetrexed intravenous infusion 500 mg/m² d2 or Liposome paclitaxel intravenous infusion 135 mg/m² d2;

Carboplatin intravenous infusion AUC5 d2; CIK cells, 1 × 10¹⁰ (10 billion), intravenous infusion, d14; Q3W.

Age 18–75 years;

Patients with stage IIIB/IIIC/IV NSCLC;

Adenocarcinoma with wild type of EGFR gene and ALK fusion gene negative can be included;

The ORR were 82.4%;

Median PFS was 19.3 months; autologous CIK cells immunotherapy in combination with sintilimab plus chemotherapy was well tolerable and showed encouraging efficacy in patients with previously untreated, advanced NSCLC.

NCT04836728

Autologous CIK cells with PD-1 inhibitor (IBI308,sintilimab) and chemotherapy A Randomized, Multicenter, Open-label Phase II Study

Stage IV NSCLC

n = 156

A Randomized, Multicenter, Open-label Phase II Study Overall survival Progression-free survival

IBI308 intravenous infusion 200 mg d1; Pemetrexed intravenous infusion 500 mg/m² d2 or Albumin paclitaxel intravenous infusion 260 mg/m² d2; Carboplatin intravenous infusion AUC5 d2; CIK cells, 1 × 10¹⁰, intravenous infusion, d14; Q3W.

Age 18–75 years; stage IV NSCLC; adenocarcinoma with wild type of EGFR gene and ALK fusion gene negative can be included.

Ongoing

CAR-T

NCT02414269

[99]

Autologous T cells genetically engineered to target the cancer-cell surface antigen mesothelin with pembrolizumab

Malignant pleural mesothelioma; non-small cell lung cancer metastatic to the pleura; breast cancer metastatic to the pleura

n = 113

Composite measure of severity and number of adverse events (AEs); response of complete response (CR); partial response (PR); and stable disease (SD);serum levels of the biomarker soluble mesothelin related peptide (SMRP) after treatment

cyclophosphamide intravenously (at 1.5 g/m²), 2–7 days before T cell infusion; Administration through the pleural catheter- On day 0 patients will be treated with genetically modified T cells. Pembrolizumab 4 weeks (+ 3/-1 week window) after completing CAR T cell administration.

Age ≥ 18 years;

Karnofsky performance status ≥ 70%; Malignant pleural mesothelioma;

non-small cell lung cancer or breast cancer metastatic to the pleura; Mesothelin expression (> 10% of the tumor expressing mesothelin) by IHC analysis; Elevated serum SMRP levels (> 1.0 nM/L).

CAR T cells were detected in peripheral blood for > 100 days in 39% of patients. Median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival, 83%). Stable disease was sustained for ≥ 6 months in 8 patients; 2 exhibited complete metabolic response on PET scan.

NCT03525782

[100]

Anti-MUC1 CAR T Cells and PD-1 Knockout Engineered T Cells

Advanced NSCLC

n = 8

Following treatment, levels of lymphocytes, IL-6, hs-CRP, PCT, CYFRA21, NSE(E), and SCC were monitored at regular intervals. Changes in tumor size were examined by MRI scans.

MUC1-specific CARs were constructed using the SM3 scFv. PD-1 gene KO in the CAR positive T cells was achieved using the CRISPR-Cas9 system and validated by sequencing. MUC1-CAR+/PD-1- KO engineered T cells at a dose of 2.5 × 10²/KG were infused over 60 min.

Age 36 to 84 years; MUC1 is expressed in malignancy tissues by immuno-histochemical (IHC); ECOG performance status of 0–1 or karnofsky performance status (KPS) score is higher than 60; Patients have a life expectancy > 12 weeks.

All patients had significant symptom improvements in the first 2 weeks after infusion. Serum CYFRA 21 declined following infusion and subsequently increased 4 weeks after treatment. In 2/6 patients, lung tumor size shrunk significantly within 4 weeks. No other adverse effects.

NCT03198052

CAR-T Cells Targeting PSCA, MUC1, TGFβ, HER2, Mesothelin, Lewis-Y, GPC3, AXL, EGFR, B7-H3 or Claudin18.2

Lung Cancer

n = 30

Number of Patients with Dose Limiting Toxicity; Percent of Patients with best response as either complete remission or partial remission; Median CAR-T cell persistence.

3 or more cycles of the CAR-T cells treatment via systemic or regional injection, from 1 × 10⁶/kg-10 × 10⁶/kg weight.

Advanced cancer that expresses PSCA, MUC1, GPC3, AXL, EGFR or B7-H3 protein; Autologous transduced T cells with greater than or equal to 20% expression of PSCA, MUC1, GPC3, AXL, EGFR or B7-H3 CAR determined by flow cytometry and killing of PSCA, MUC1, GPC3, AXL, EGFR, or B7-H3-positive targets greater than or equal to 20% in cytotoxicity assay.

Recruiting

NCT04503980

αPD1-MSLN-CAR T Cells [107]

MSLN-positive advanced solid tumors

n = 10

Maximum tolerated dose (MTD); Objective response rate (ORR); Progression-free survival (PFS); Overall survival (OS); Peak Plasma Concentration (Cmax); Pharmacodynamics (PD).

Four doses of CAR T cells will be evaluated in this study:

1 × 10⁵ CAR⁺ T cells/kg,

3 × 10⁵ CAR⁺ T cells/kg,

1 × 10⁶ CAR⁺ T cells/kg,

3 × 10⁶ CAR⁺ T cells/kg.

Age 18-70 years; advanced solid tumors; ECOG performance status of 0 or 1; Staining of MSLN must be greater than 50%; of the cells in the tumor tissue, apparent expressing in the membrane; PD-L1 expression must be positive.

The total objective response rate was 63.64%. All enrolled patients are still alive. The longest PFS was up to 26 months. Median follow-up was four months.