Production, safety and antitumor efficacy of recombinant Oncofetal Antigen/immature laminin receptor protein.

Abstract:

:We describe here for the first time an efficient high yield production method for clinical grade recombinant human Oncofetal Antigen/immature laminin receptor protein (OFA/iLRP). We also demonstrate significant antitumor activity for this protein when administered in liposomal delivery form in a murine model of syngeneic fibrosarcoma. OFA/iLRP is a therapeutically very promising universal tumor antigen that is expressed in all mammalian solid tumors tested so far. We have cloned the human OFA/iLRP cDNA in a bacterial expression plasmid which incorporates a 6x HIS-tag. Large scale cultures of the plasmid transformed Escherichia coli were performed and the crude HIS-tagged OFA/iLRP was isolated as inclusion bodies and solubilized in guanidine chloride. The protein was then purified by successive passage through three column chromatography steps of immobilized metal affinity, anion exchange, and gel filtration. The resulting protein was 94% pure and practically devoid of endotoxin and host cell protein. The purified OFA/iLRP was tested in mice for safety and efficacy in tumor rejection with satisfactory results. This protein will be used for loading onto autologous dendritic cells in an FDA approved phase I/II human cancer vaccine trial in OFA/iLRP-positive breast cancer patients.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Barsoum AL,Liu B,Rohrer JW,Coggin JH Jr,Tucker JA,Pannell LK,Schwarzenberger PO

doi

10.1016/j.biomaterials.2009.02.022

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

3091-9

issue

17

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(09)00182-3

journal_volume

30

pub_type

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