A Study of Combinations of D-CIK Immunotherapy And Anti-PD-1 In Refractory Solid Tumors

Background: Combinations of dendritic and cytokine-induced killer cell (D-CIK) based adoptive immunotherapy and anti-PD-1 antibody may enhance the immune response and stop cancer cells from growing. Objective: Phase II clinical trial to investigate the safety, clinical activity and toxicity of combinations of D-CIK and anti-PD-1 antibody in patients with treatment-refractory solid tumors. Methodology: Phase II clinical trial in patients with advanced metastatic hepatocellular carcinoma, renal cell carcinoma,bladder cancer,colorectal cancer,non-small-cell lung cancer,breast cancer and other solid cancers. The D-CIK was isolated from peripheral blood of participants,then activated,expanded and incubated with anti-PD-1 antibody before infusion. The enough number (1.0-1.5 \*10\^10 cells) of D-CIK were infused back into participants.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* Participantswith treatment-refractory advanced hepatocellular carcinoma, renal cell carcinoma,bladder cancer,colorectal cancer,non-small-cell lung cancer,breast cancer and other solid cancers.
* Age 18 to 75 years.
* Willing to sign a durable power of attorney.
* Able to understand and sign the Informed Consent Document.
* Life expectancy of greater than three months.
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the preparative regimen.
* Adequate organ function.
* Serology:

  * Seronegative for HIV antibody.
  * Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
* Hematology:

  * WBC (\> 3000/mm(3)).
  * Platelet count greater than 100,000/mm(3).
  * Hemoglobin greater than 8.0 g/dl.
* Chemistry:

  * Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
  * Serum creatinine less than or equal to 1.6 mg/dl.
  * Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.

Exclusion Criteria:

* Previous treatment with anti-CTLA-4 and anti-PD-1/PD-L1.
* Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
* Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
* History of autoimmune disease
* Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
* Concurrent antineoplastic therapies and systemic steroid therapy.

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