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Recombinant interleukin-2-activated intracavitary lymphocytes: phenotypic characteristics and effector function.
T Umiel1, J Monselise, T Klein
1Department of Pediatric Hematology and Oncology, Tel-Aviv University, Petah-Tikva, Israel.
Journal of Biological Response Modifiers
|August 1, 1989
Summary
Intracavitary lymphocytes (ICL) from cancer patients, when activated with recombinant interleukin-2 (rIL-2), gain potent antitumor activity. This preclinical study supports ICL as a promising candidate for adoptive immunotherapy trials in ovarian carcinoma.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Malignant effusions contain intracavitary lymphocytes (ICL) with potential antitumor properties.
- Adoptive immunotherapy offers a promising avenue for cancer treatment, particularly for ovarian carcinoma.
Purpose of the Study:
- To evaluate the antitumor potential of ICL from cancer patients.
- To establish a baseline for developing adoptive immunotherapy trials for ovarian carcinoma.
Main Methods:
- Assessed functional cytolytic activity of fresh and rIL-2-activated ICL.
- Analyzed phenotypic characteristics of ICL.
- Utilized NK-sensitive (K562) and NK-resistant (Daudi) targets, alongside fresh tumor cells.
Main Results:
- Fresh ICL showed spontaneous activity against NK-sensitive targets but limited activity against NK-resistant targets and tumor cells.
- rIL-2 activation significantly enhanced ICL cytolytic activity against NK-resistant targets and augmented NK activity.
- Activated ICL exhibited non-MHC-restricted antitumor activity, resembling lymphokine-activated killer (LAK) cells.
- Phenotypic analysis revealed rIL-2 induced enrichment in NKH1+, CD8+, and VLA-1+ cells, correlating with peak cytolytic activity.
- CD4 depletion from activated ICL enhanced cytolytic activity.
Conclusions:
- rIL-2 activation of ICL generates significant killer activity against NK-resistant and fresh tumor targets.
- Enrichment of NKH1, CD8, and VLA-1 expression on ICL is associated with enhanced effector function.
- ICL represents a viable cellular component for developing adoptive immunotherapy strategies for ovarian cancer.