Phase Ⅰ clinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma

Cancer Biol Ther. 2011 Mar 1;11(5):450-6. doi: 10.4161/cbt.11.5.14669. Epub 2011 Mar 1.

Abstract

Background and aims: To observe safety and influence on viral load and peripheral T lymphocyte subsets of combination therapy with percutaneous microwave ablation (PMWA) and adoptive immunotherapy in hepatocellular carcinoma (HCC) with hepatitis B.

Results: No adverse effects of grade Ⅲ/Ⅳ were observed. Viral load was decreased in 57.14% (four of seven) of patients and was undetectable in two (28.6%) patients without antiviral therapy. The percentage of CD4(+)CD25(high) regulatory T lymphocytes decreased significantly, and the percentage of CD8(+)CD28(-) effector cells increased significantly 1 month after therapy. However, 6 months after therapy, there was no significant difference.

Methods: Ten HCC (D≤5 cm, fewer than 3 tumors) patients were treated with radical PMWA and three courses of immunotherapy, which were started with PMWA, 2 weeks post-PMWA, and 3 months after PMWA. Peripheral blood mononuclear cells were differentiated into phenotypically confirmed DCs and effector cells. Immature DCs, cytokine-induced killer cells (CIK) and cytotoxic T lymphocytes (CTL) were injected into the marginal area of ablated tumors under contrast-enhanced sonographic guidance. Under sonographic guidance, tumor lysate-pulsed DC was injected into groin lymph nodes, while DC-CIK and CTL were injected into the abdominal cavity. CIK was infused intravenously.

Conclusion: Adoptive immunotherapy prescribed soon after PMWA for HCC patients was safe and ameliorated the percentage of peripheral lymphocytes.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ablation Techniques*
  • Adult
  • Aged
  • CD28 Antigens / analysis
  • CD28 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / therapy*
  • Combined Modality Therapy
  • Cytokine-Induced Killer Cells / immunology
  • Dendritic Cells / immunology
  • Hepatitis B / complications*
  • Humans
  • Immunotherapy, Adoptive*
  • Interleukin-2 Receptor alpha Subunit / analysis
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Leukocytes, Mononuclear / immunology
  • Liver Neoplasms / complications
  • Liver Neoplasms / therapy*
  • Male
  • Microwaves / therapeutic use*
  • Middle Aged
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / radiation effects
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Load / radiation effects

Substances

  • CD28 Antigens
  • Interleukin-2 Receptor alpha Subunit