Reactivation of murine tumour-infiltrating lymphocytes with solid-phase anti-CD3 antibody: in vitro cytokine production is associated with in vivo efficacy
| Autor: | D.L. Leonard-Vidal, Peter S. Goedegebuure, James C. Cusack, L. M. Douville, M. Zuber, Maximilian P. Chang, Ulrike L. Burger, Timothy J. Eberlein |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Cytotoxicity
Immunologic Lung Neoplasms CD3 Complex medicine.drug_class medicine.medical_treatment Fluorescent Antibody Technique chemical and pharmacologic phenomena Biology Monoclonal antibody Immunotherapy Adoptive Immunophenotyping Interferon-gamma Mice Lymphocytes Tumor-Infiltrating In vivo Tumor Cells Cultured medicine Animals Interferon gamma Antibodies Monoclonal Granulocyte-Macrophage Colony-Stimulating Factor hemic and immune systems Immunotherapy Cytotoxicity Tests Immunologic In vitro Mice Inbred C57BL Cytokine Granulocyte macrophage colony-stimulating factor Oncology Antigens Surface Immunology Monoclonal Cancer research Cytokines Interleukin-2 Female Surgery Sarcoma Experimental Cell Division medicine.drug |
| Zdroj: | Surgical Oncology. 3:79-89 |
| ISSN: | 0960-7404 |
| DOI: | 10.1016/0960-7404(94)90003-5 |
| Popis: | Previously we described the use of solid-phase anti-CD3 monoclonal antibody (mAb) to stimulate murine tumour-infiltrating lymphocytes (TIL) and their subsequent expansion in recombinant interleukin 2 (rIL-2). In a pulmonary metastases model using the methylcholanthrene-induced sarcoma MCA-105 anti-CD3 activated TIL were capable of eradicating disease similar to TIL cultured in rIL-2 only. Here we extend these observations by characterizing the biological effects of sequential solid-phase anti-CD3 activation. TIL from MCA-105 tumour activated with solid-phase anti-CD3 on day 1 were reactivated on day 14, or day 26, or both and compared to TIL grown in rIL-2 only or TIL activated with anti-CD3 once on day 1. Reactivation enhanced in vitro proliferation 1.8- to 4-fold compared to TIL activated once with anti-CD3 (P < 0.05). In addition, the total lytic capacity of the cultures was enhanced after reactivation without changing the phenotype of the TIL cultures. Reactivation resulted in a greater in vivo efficacy when the TIL were administered within 72 h of reactivation. In contrast, TIL activated with anti-CD3 on day 1 and day 14 were least effective of all TIL cultures (P < 0.05). This correlated with in vitro cytokine production. The most effective TIL cultures in vivo produced 4- to 100-fold higher amounts of cytokines, especially interferon gamma (IFN gamma) and granulocyte macrophage colony stimulating factor (GM-CSF), than the other cultures. On the other hand, the least effective in vivo TIL culture, TIL activated with anti-CD3 on day 1 and 14, produced little or no cytokines. These data suggest that in vitro production of cytokines is indicative of in vivo efficacy of anti-CD3 activated TIL. |
| Databáze: | OpenAIRE |
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