Infusion of Autologous Alloactivated Lymphocytes in Melanoma Patients: Toxicity and Immunologic Monitoring

1986 ◽  
Vol 72 (4) ◽  
pp. 383-388 ◽  
Author(s):  
Carlo Gambacorti-Passerini ◽  
Raffaele Marolda ◽  
Gabriella Tona ◽  
Gianalfredo Sciorelli ◽  
Giuseppe Fossati ◽  
...  

Previous work has shown that infusion of autologous helper-enriched, alloactivated lymphocytes in melanoma patients may induce, in addition to other mild signs of toxicity, a transient but sharp elevation of blood pressure. To avoid such a disturbing symptom, the in vitro protocol of peripheral blood lymphocyte activation has been modified. In the present study we show that such a modification has led to a lower toxicity of autologous lymphocyte infusion in 4 melanoma patients; in particular, hypertension was no longer observed. In addition, an immunologic monitoring was carried out in these patients. In 1 of 4 patients the treatment enhanced the in vitro cytotoxic activity of peripheral blood lymphocytes against autologous tumor cells. Other parameters such as NK activity and T4/T8 ratio did not show significant trends. The possible implications of these findings for clinical trials of adoptive immunotherapy with lymphocytes are discussed.

1993 ◽  
Vol 37 (3) ◽  
pp. 175-180 ◽  
Author(s):  
Jonathan R. Sporn ◽  
Michael T. Ergin ◽  
Gerald R. Robbins ◽  
Ritchard G. Cable ◽  
Herbert Silver ◽  
...  

Cytokine ◽  
2017 ◽  
Vol 96 ◽  
pp. 30-40 ◽  
Author(s):  
Katarina M. Mirjačić Martinović ◽  
Ana M. Vuletić ◽  
Nada Lj. Babović ◽  
Radan R. Džodić ◽  
Gordana M. Konjević ◽  
...  

1994 ◽  
Vol 3 (5) ◽  
pp. 341-346
Author(s):  
S. B. Cheknev ◽  
Y. G. Ashmanova ◽  
A. D. Pritsker ◽  
O. L. Latysheva ◽  
F. I. Yershov ◽  
...  

Thein vitroaction of interferon (IFN)-α and IFN-γ from six healthy donors and ten patients with multiple sclerosis (MS) on natural killer (INK) activity of peripheral blood lymphocytes (PBL) was studied in an autologous system. The NK activity of PBL was detected by a cytotoxic test using3H-uridine human erythromyeloblast K562 cells. Autologous IFN-α and IFN-γ did not augment NK activity of PBL from healthy donorsin vitro, whereas in samples from MS patients the IFNs strongly stimulated NK cell cytotoxic function. This stimulation suggests the existence of an inhibitor of regulatory IFN action, that is produced in healthy donors simultaneously with IFN in response to IFN induction, but which is lacking in commercial IFN preparations. The factor-containing supernatants from healthy donors reduced the stimulatory action of autologous IFNs in patients with MS almost until complete blockade. Because this inhibitor was absent in patients with MS, deficiency of an inhibitor of IFN regulatory action in MS could open the way to treatment of this compartment of the immune system.


Neurosurgery ◽  
1991 ◽  
Vol 28 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Kevin O. Lillehei ◽  
Dawn H. Mitchell ◽  
Stephen D. Johnson ◽  
Larry E. McCleary ◽  
Carol A. Kruse

Abstract Between August 1986 and October 1987, the Denver Brain Tumor Research Group conducted a clinical trial using autologous human recombinant interleukin-2 (rIL-2)-activated lymphocytes to treat 20 patients with recurrent high-grade gliomas. The trial involved surgical resection and/or decompression followed by intracavitary implantation of lymphokine-activated killer (LAK) cells and autologous stimulated lymphocytes (ASL) along with rIL-2 in a plasma clot. One month later, stimulated lymphocytes and rIL-2 were infused through a Rickham reservoir attached to a catheter directed into the tumor bed. The LAK cells were rIL-2-activated peripheral blood lymphocytes cultured for 4 days; the ASL were lectin- and rIL-2-activated peripheral blood lymphocytes cultured for 10 days. Of the 20 patients treated, 11 were evaluated as a group (mean age, 44 years, range, 15-61 years; mean Karnofsky rating, 69, range, 50-100; mean Decadron dose at entry, 14 mg/d. range, 0-32). The average number of lymphocytes implanted was 7.6 × 109 (range, 1.9-27.5 × 109), together with 1 to 4 × 106 U of rIL-2. To date, 10 of the 11 patients died, all from recurrent tumor growth. The median overall survival time was 63 weeks (range, 36-201; mean, 86). The median survival time after immunotherapy was 18 weeks (range, 11-151; mean, 39). No significant difference in survival after immunotherapy was found between those patients who had received previous chemotherapy and those who had not. The use of steroids or prior chemotherapy did not influence the in vitro generation of ASL or LAK cells. Prior chemotherapy did correlate, however, with diminished in vitro cytotoxicity against the natural killer-sensitive (K562) target cell by LAK cells (P < 0.05) but not that by ASL. There were no major adverse side effects. Although adoptive immunotherapy was safe and well tolerated, its therapeutic potential remains in question.


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