Abstract
Three intraperitoneal human ovarian cancer xenografts (OS, HU, and LA) were used to assess the antitumour activity of intraperitoneal therapy with liposome encapsulated MTP-PE. MTP-PE led to significant prolongation of survival in all three xenograft models, but with varying efficacy. In one tumour model (OS), 80% of mice were cured of tumour by twice weekly therapy for 4 weeks, whereas in another xenograft model (LA), the median survival time was approximately doubled compared to PBS injected and placebo liposome injected controls (median survivals: 30 vs 62.5 days respectively). The antitumor efficacy of MTP-PE did not correlate with the extent of peritoneal neutrophil infiltration after intraperitoneal therapy. Combined therapy with liposome encapsulated MTP-PE and recombinant murine granulocyte-macrophage colony stimulating factor led to increased survival of mice bearing the LA and HU xenografts, compared to tumour bearing mice treated with either agent singly.
Highlights
MTP-PE significantly prolonged the survival of mice bearing the LA and OS xenografts compared to PBSA or placebo liposome injected mice (P
The median survival and the number of mice surviving greater than 60 days was greater in the groups injected with liposome encapsulated MTP-PE compared to the groups injected with the placebo liposomes, the difference in the survival between the two groups was not statistically significant in the HU xenograft
The results presented here are the first to show the efficacy of locally administered liposome-encapsulated MTP-PE in the treatment of human cancer xenografts
Summary
Methods and materialsXenografts and mice6-12 week old specific pathogen free athymic (nu/nu) female mice of mixed genetic background were used. The OS and HU tumours were taken from 51 year old and 23 year old patients at the time of the first laparotomy respectively. Both the OS and HU tumours were moderately differentiated serous cystadenocarcinomas. The LA xenograft was established from a primary poorly differentiated mucinous cystadenocarcinoma in a 71 year old patient. The xenografts were stable in their growth characteristics between the passages listed. The LA xenograft, started to exhibit a more rapid growth rate after passage 32, and in one experiment this aggressive tumour was used to assess the therapeutic effect of MTP and muGMCSF
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