Inpharma 1317 - 8 Dec 2001

CEA-based DNA vaccine exhibitspromising antitumour activity

A DNA vaccine encoding human carcinoembryonicantigen (CEA) in conjunction with monoclonal antibodyKS1-4-IL-2 conjugate exhibited promising antitumouractivity against a CEA-expressing Lewis lung carcinoma(LLC-CEA-KSA) cell line in a murine model, reportresearchers from the US.

In this study, CEA transgenic mice received a total of 3oral immunisations at 2-week intervals, with aSalmonella typhimurium vector harbouring the activevaccine (containing the entire CEA human gene; pW-CEA) or an inactive control (pER-CEA). Unimmunisedanimals acted as another group of controls. All animalswere challenged with a lethal dose of LLC-CEA-KSA cellsinjected either subcutaneously, or intravenously toinduce pulmonary metastases, 2 weeks after the lastimmunisation. Selected animals also received IVmonoclonal antibody KS1-4-IL-2 conjugate for 5 days,starting 24 hours after tumour challenge.

Treatment with pW-CEA alone reduced SC tumourcell growth to approximately 25% of that seen inunimmunised controls, and prevented pulmonarymetastases developing in 2 of 8 animals. However,combination therapy with pW-CEA and monoclonalantibody KS1-4-IL-2 conjugate resulted in completeregression of all SC tumours in all 8 animals andprevented the development of pulmonary metastases in6 of 8 animals. Treatment with pER-CEA alone, or incombination with monoclonal antibody KS1-4-IL-2conjugate, had no significant inhibitory effect whencompared with unimmunised controls.

The researchers conclude that these findings suggestthat ‘combinations of DNA vaccines with suchimmunocytokines may lead to improved treatments forlung cancer’.Niethammer AG, et al. An oral DNA vaccine against human carcinoembryonicantigen (CEA) prevents growth and dissemination of Lewis lung carcinoma inCEA transgenic mice. Vaccine 20: 421-429, 12 Nov 2001 800885975

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Inpharma 8 Dec 2001 No. 13171173-8324/10/1317-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved