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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1997-9-10
|
| pubmed:abstractText |
Autologous transplantation can induce extended remission in some patients with advanced breast cancer and lymphoma yet nearly 80% and 50%, respectively, will ultimately relapse. In vitro studies suggest that activated natural killer cells (NK) mediate lytic activity against breast cancer and lymphoma cell lines. Therefore, immunotherapy with interleukin-2 (IL-2, Amgen) to activate NK may improve long-term disease-free survival when administered in a post-transplant minimal residual disease setting. To determine the feasibility of administering IL-2 and activation of NK post-transplant, twelve patients (6 breast cancer, 6 lymphoma) were enrolled on a phase I dose escalation study after autologous transplantation (median day + 94, range 50-166). IL-2 was self administered at 0.25 x 10(6) (n = 6) or 0.5 x 10(6) (n = 6) U/m2/day subcutaneously for 84 consecutive days. The best tolerated dose was 0.25 x 10(6) U/m2/day (75% of planned doses given vs. 48% at the higher dose). Dose limiting toxicity occurred in 6 patients (n = 2 at 0.25 x 10(6) U/m2/day, n = 4 at 0.5 x 10(6) U/m2/day) consisting of decreased performance status (n = 2), thrombocytopenia (n = 3, 1 at the lower dose), and mild neutropenia (n = 1 at the lower dose). However, all symptoms resolved within a week following discontinuation of IL-2 and no patient required hospitalization. Circulating soluble IL-2 receptor levels were significantly increased in all patients receiving IL-2. Patients receiving at least 28 days of IL-2 exhibited a greater than 10-fold increment in circulating CD56+bright/CD3- NK. Furthermore, lytic function was increased against NK resistant targets, MCF-7 (breast cancer), and Raji (lymphoma). In vivo IL-2 primed NK cells obtained by lymphapheresis were activated in large-scale ex vivo incubation in high dose IL-2 (1,000 U/mL) at high cell density (10 x 10(6)/mL), in gas permeable bags, and using serum-free media. NK lytic function against MCF-7 and Raji targets was further enhanced. We conclude that low dose subcutaneous IL-2 based immunotherapy is feasible, relatively safe, can be administered in an outpatient setting and hypothesize that additional ex vivo incubation in IL-2 may be used to generate NK cells with potent antitumor effects in vivo.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
1083-8791
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
3
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
34-44
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9209739-Adjuvants, Immunologic,
pubmed-meshheading:9209739-Adult,
pubmed-meshheading:9209739-Bone Marrow Transplantation,
pubmed-meshheading:9209739-Breast Neoplasms,
pubmed-meshheading:9209739-Cells, Cultured,
pubmed-meshheading:9209739-Cytokines,
pubmed-meshheading:9209739-Cytotoxicity, Immunologic,
pubmed-meshheading:9209739-Female,
pubmed-meshheading:9209739-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:9209739-Humans,
pubmed-meshheading:9209739-Injections, Subcutaneous,
pubmed-meshheading:9209739-Interleukin-2,
pubmed-meshheading:9209739-Killer Cells, Natural,
pubmed-meshheading:9209739-Lymphocyte Activation,
pubmed-meshheading:9209739-Lymphoma,
pubmed-meshheading:9209739-Male,
pubmed-meshheading:9209739-Middle Aged,
pubmed-meshheading:9209739-Self Administration,
pubmed-meshheading:9209739-Transplantation, Autologous,
pubmed-meshheading:9209739-Treatment Outcome,
pubmed-meshheading:9209739-Tumor Cells, Cultured
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Low dose subcutaneous interleukin-2 after autologous transplantation generates sustained in vivo natural killer cell activity.
|
| pubmed:affiliation |
Department of Medicine, University of Minnesota, Minneapolis, USA.
|
| pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Clinical Trial, Phase I
|