Augmentation of the therapeutic efficacy of adoptive tumor immunotherapy by in vivo administration of slowly released recombinant interleukin 2

1986 ◽  
Vol 21 (1) ◽  
Author(s):  
Takashi Nishimura ◽  
Yuji Togashi ◽  
Makiko Goto ◽  
Hideki Yagi ◽  
Yasushi Uchiyama ◽  
...  
1987 ◽  
Vol 165 (3) ◽  
pp. 650-656 ◽  
Author(s):  
M J Reddehase ◽  
W Mutter ◽  
U H Koszinowski

We have shown in a murine model system for cytomegalovirus (CMV) disease in the immunocompromised host that in vivo application of recombinant human IL-2 (rhIL-2) can enhance the antiviral effect of a limited number of CD8+T lymphocytes, not only in prophylaxis, but also in therapy, when virus has already colonized host tissues. The observed net effect of IL-2 was consistent with the assumption of daily effector population doublings. The prospects for IL-2-supported immunotherapy of established CMV infection depend upon the tissues involved in disease. It appears that the prospects for controlling established CMV adrenalitis are less promising than for a therapy of interstitial CMV pneumonia.


Author(s):  
Carlo Riccardi ◽  
Graziella Migliorati ◽  
Antonio Giampietri ◽  
Lorenza Cannarile ◽  
Emira Ayroldi ◽  
...  

1996 ◽  
Vol 32 ◽  
pp. S5
Author(s):  
N. Finnegan ◽  
H.P. Redmond ◽  
M. Da Costa ◽  
D. Bouchier-Hayes

1987 ◽  
Vol 9 (3) ◽  
pp. 307-312 ◽  
Author(s):  
Mark Lyte ◽  
Robert H. Blanton ◽  
Michael J. Myers ◽  
Peter H. Bick

1994 ◽  
Vol 17 (1) ◽  
pp. 50-54 ◽  
Author(s):  
Tetsu Shinkai ◽  
Tomohide Tamura ◽  
Tetsuro Sano ◽  
Akira Kojima ◽  
Kenji Eguchi ◽  
...  

1982 ◽  
Vol 155 (4) ◽  
pp. 968-980 ◽  
Author(s):  
M A Cheever ◽  
P D Greenberg ◽  
A Fefer ◽  
S Gillis

Spleen cells from C57BL/6 mice immunized in vivo with a syngeneic Friend virus-induced leukemia, FBL-3, were specifically activated by culture for 7 d with FBL-3, then nonspecifically induced to proliferate in vitro for 12 d by addition of supernatants from concanavalin A-stimulated lymphocytes containing interleukin 2 (IL-2). Such long-term cultured T lymphocytes have previously been shown to specifically lyse FBL-3 and to mediate specific adoptive therapy of advanced disseminated FBL-3 when used as an adjunct to cyclophosphamide (CY) in adoptive chemoimmunotherapy. Because the cultured cells are dependent upon IL-2 for proliferation and survival in vitro, their efficacy in vivo is potentially limited by the availability of endogenous IL-2. Thus, the aim of the current study was to determine whether exogenously administered purified IL-2 could augment the in vivo efficacy of long-term cultured T lymphocytes. Purified IL-2 alone or as an adjunct to CY as ineffective in tumor therapy. However, IL-2 was extremely effective in augmenting the efficacy of IL-2-dependent long-term cultured T lymphocytes in adoptive chemoimmunotherapy. The mechanism by which IL-2 functions in vivo is presumably by promoting in vivo growth and/or survival of adoptively transferred cells. This assumption was supported by the findings that IL-2 did not enhance the modest therapeutic efficacy of irradiated long-term cultured cells that were incapable of proliferating in the host and was ineffective in augmenting the in vivo efficacy of noncultured immune cells that are not immediately dependent upon exogenous IL-2 for survival.


1994 ◽  
Vol 86 (6) ◽  
pp. 671-675 ◽  
Author(s):  
Kenneth G. M. Park ◽  
Steven D. Heys ◽  
Margaret A. McNurlan ◽  
Peter J. Garlick ◽  
Oleg Eremin

1. The ‘flooding’ dose technique was used to measure rates of lymphocyte protein synthesis after infusion of [1-13C]leucine (20 atoms% enrichment, 4 g/70 kg body weight). Lymphocyte protein synthesis was measured in healthy subjects and in patients with metastatic colorectal cancer before and during infusion of recombinant interleukin-2. Rates of protein synthesis were compared with thymidine uptake in vitro and phenotypic analysis of lymphocytes. 2. The median rate of lymphocyte protein synthesis in four healthy subjects was 9% (range 7.2–11.4%/day) and in seven patients with colorectal cancer was 6.4% (range 4.2–8.2%/day). After recombinant interleukin-2 treatment the median rate of lymphocyte protein synthesis was 27.8% (range 25.2–33.7%/day). 3. The increased rates of lymphocyte protein synthesis in vivo, after recombinant interleukin-2 infusion, corresponded with increased rates of thymidine uptake and changes in the phenotypic expression of lymphocytes, but these were less consistent than the measured rates of protein synthesis. 4. It is concluded that lymphocyte activation is accompanied by a marked increase in lymphocytic protein synthesis which may have important implications for whole body protein metabolism. Furthermore, measurement of lymphocyte protein synthesis may provide a determination of lymphocyte activation in vivo.


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