The long term objective of this proposal is to examine the effect of adoptive T cell transfers in altering immune responsiveness in cancer patients. We are proposing a Phase II clinical trial for the treatment of adenocarcinoma of the lung by intravenous infusion of Interleukin 2-responsive T lymphocytes and systemic Interleukin 2 (IL 2). The lymphocytes to be used in this therapy are tumor infiltrating cells propagated directly from autologous tumor tissue. Two color flow cytometric analyses will be carried out to characterize these lymphocytes and to compare them to lymphocytes derived from blood and pleural fluid from the same patient. The lymphocytes used for therapy will be assessed for functional activity by several criteria including the ability to lyse and respond to autologous tumor when it is available. Patients will receive 1 x 10-10 lymphocytes over a 3 week period during which time they will receive continuous intravenous infustions of 1,000,000 units of recombinant IL 2/M2/24 hours. Patient will be monitored by routine medical and radiographic testing. The IL 2-propagated lymphocytes will be radiolabelled in order to assess the in vivo distribution of these cells. Monitoring of surface phenotypes and functional assessment of changes in peripheral blood lymphocytes will be carried out during therapy. Each patient will receive a second course of therapy following a 30 day interval. Patients will be re-evaluated for evidence of decrease in tumor burden and alterations in immunological parameters.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA043244-03
Application #
3185377
Study Section
Experimental Therapeutics Subcommittee 2 (ET)
Project Start
1986-07-15
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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Kradin, R L; Kurnick, J T; Preffer, F I et al. (1989) Adoptive immunotherapy with IL-2 results in the loss of delayed-type hypersensitivity responses and the development of immediate hypersensitivity to recall antigens. Clin Immunol Immunopathol 50:184-95
Kradin, R L; Kurnick, J T; Lazarus, D S et al. (1989) Tumour-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. Lancet 1:577-80

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