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Dualistic effects of cis‐diammine‐dichloro‐platinum on the anti‐tumor efficacy of subsequently applied recombinant interleukin‐2 therapy: A tumor‐dependent phenomenon
Author(s) -
Bernsen Moniquc R.,
Heintz A. Peter M.,
Van Barungen Harrold J. J.,
Van Der Velden Alike W.,
Dullens Hub F. J.,
Otter Willem Den
Publication year - 1993
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910540326
Subject(s) - cisplatin , in vivo , combination therapy , immune system , medicine , pharmacology , interleukin 2 , chemotherapy , in vitro , cancer research , immunotherapy , immunology , chemistry , biology , biochemistry , microbiology and biotechnology
The efficacy with which disseminated SL2 and P815 tumors, in syngeneic DBA/2 mice, can be eradicated with low‐dose recombinant interleukin‐2 (rlL‐2) therapy is about equal. Treatment (i.p.) of DBA/2 mice, injected i.p. with SL2 or P8I5 cells on day 0, with rlL‐2 (Proleukin) on days 10 to 14 results in a cure rate of 50 to 60% in each case. The in vitro sensitivity of SL2 and P8I5 cells to cis‐diammine‐dichloro‐platinum [II] (cisplatin) is also comparable, although P8I5 appears to be slightly more sensitive. In vivo , however, therapy with cisplatin is far less effective against P8I5 than against SL2. In the DBA/2‐SL2 model, at all doses tested, combination therapy with cisplatin (administered on day 2) and rlL‐2 (administered on days 10–14) resulted in anti‐tumor efficacy greater than that of either drug separately. In contrast, in the DBA/2‐P8I5 model, cisplatin decreased the anti‐tumor efficacy of subsequently applied rlL‐2 therapy. As the only difference between the 2 tumor models is the tumor itself, the success of combination therapy with cisplatin and rlL‐2 was dependent on tumor characteristics. We suggest that in these 2 tumor models, neither the sensitivity of these tumors to cisplatin nor their growth and dissemination patterns were responsible for the contrasting results of combination therapy in these models. Instead, tumor‐dependent immune‐modulating effects of cisplatin may be the cause of these effects. These immune‐modulating effects may comprise (a) effects of cisplatin on the tumor cells, resulting in changes in their susceptibility to immune effector cells, or changes in their immunogenicity; (b) activating or suppressive effects of cisplatin on immune effector cells; or (c) a combination of these effects. These effects could then either synergize or antagonize with the immune activating properties of rlL‐2.