Treatment with HPMA copolymer-based doxorubicin conjugate containing human immunoglobulin induces long-lasting systemic anti-tumour immunity in mice

Cancer Immunology, Immunotherapy : CII
Milada SírováBlanka Ríhová

Abstract

Linkage of doxorubicin (Dox) to a water-soluble synthetic N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) eliminates most of the systemic toxicity of the free drug. In EL-4 lymphoma-bearing C57BL/6 mice, a complete regression of pre-established tumours has been achieved upon treatment with Dox-PHPMA-HuIg conjugate. The treatment was effective using a range of regimens and dosages, ranging from 62.5 to 100% cured mice treated with a single dose of 10-20 mg of Dox eq./kg, respectively. Fractionated dosages producing lower levels of the conjugate for a prolonged time period had substantial curative capacity as well. The cured mice developed anti-tumour protection as they rejected subsequently re-transplanted original tumour. The proportion of tumour-protected mice inversely reflected the effectiveness of the primary treatment. The treatment protocol leading to 50% of cured mice produced only protected mice, while no mice treated with early treatment regimen (i.e. starting on day 1 after tumour transplantation) rejected the re-transplanted tumour. Exposure of the host to the cancer cells was a prerequisite for developing protection. The anti-tumour memory was long lasting and specific against the original tumour, as the cured m...Continue Reading

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Citations

Jan 13, 2009·Bioconjugate Chemistry·Ningning YangRam I Mahato
Dec 13, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Milada ŠírováTomáš Etrych
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Jun 4, 2010·Molecular Pharmaceutics·Tomás EtrychKarel Ulbrich
Jun 18, 2011·Veterinary Parasitology·Juan M IracheSocorro Espuelas

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