Immune Modulation in Cancer Patients After Adoptive Transfer of Anti-CD3/Anti-CD28–Costimulated T Cells—Phase I Clinical Trial
| Autor: | Lawrence G. Lum, John P. Hanson, Ann V. Lefever, Jonathan Treisman, Nina Garlie |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Adult
Cytotoxicity Immunologic Cancer Research Adoptive cell transfer CD3 Complex T-Lymphocytes medicine.medical_treatment Immunology Lymphocyte Activation Immunotherapy Adoptive Peripheral blood mononuclear cell Immunophenotyping Interferon-gamma Immune system CD28 Antigens Neoplasms medicine Humans Immunology and Allergy Cells Cultured Aged Pharmacology Tumor Necrosis Factor-alpha business.industry Granulocyte-Macrophage Colony-Stimulating Factor Immunotherapy Middle Aged Granulocyte macrophage colony-stimulating factor Cytokine Leukocytes Mononuclear Cytokines Tumor necrosis factor alpha Interleukin-4 business CD8 medicine.drug |
| Zdroj: | Journal of Immunotherapy. 24:408-419 |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/00002371-200109000-00003 |
| Popis: | Anti-CD3/anti-CD28 monoclonal antibody-coactivated T cells (COACTs) proliferate, secrete tumoricidal cytokines, and mediate non-major histocompatibility complex (MHC)-restricted cytotoxicity. This phase I study was done to determine the safety, maximum tolerated dose, technical limits of expansion, and modulation of immune functions in cancer patients given COACTs. Coactivated T cells were produced by stimulating peripheral blood mononuclear cells (PBMCs) with OKT3 anti-CD3 and 9.3 (anti-CD28)-coated beads in the presence of 100 IU interleukin (IL)-2 per milliliter for 14 days. The beads were removed after 4 days of culture. Ten courses of COACTs were given to eight patients with renal cell (1), ovarian (2), breast (1), and colorectal (4) carcinomas; two patients received two courses of COACTs. Patients were given up to 10 x 10 9 COACTs twice a week for 3 weeks without dose-limiting toxicities. Patients at the first and second dose levels received a mean total of 17.6 and 42.4 x 10 9 COACTs, respectively. After 14 days of culture, the COACTs contained a mean of 57.5% CD4 + cells and 42.5% CD8 + cells, exhibited non-MHC-restricted cytotoxicity, and produced significant amounts of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and granulocyte macrophage colony-stimulating factor (GM-CSF). Infusions were safe and induced measurable serum levels of IFNgamma, TNFalpha, and IL-4 in two patients. Peripheral blood mononuclear cells from patients who received COACTs secreted higher amounts of IFNgamma and GM-CSF on in vitro anti-CD3/anti-CD28 restimulation than PBMCs obtained before immunotherapy. The detection of cytokines in patient sera and enhanced in vitro production of cytokines by anti-CD3/anti-CD28-stimulated patient PBMCs after COACT infusions suggest that COACTs were modulating immune responses in cancer patients. |
| Databáze: | OpenAIRE |
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