SMANCS

T. Konno and H. Maeda, Targeting chemotherapy of hepatocellular carcinoma Arterial administration of SMANCS/Lipiodol, in Neoplasm in the Liver (K. Okada and K. G. Ishak, eds.), Springer-Verlag, New York, 1987, p. 343. 

Matsumura, Y, and Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res., 1986, 46, 6387-6392. 

Poly(styrene- Neocar- Renal cell Improved survival, SMANCS dissolved in [93]... 

SMANCS (Styrere-co-maleic acid/anhydride polymer bound to neocarzinostatin Neocarzinostatin (an antitumor protein) Amide bond between polymer carboxyl and protein amino None N/A SMANCS showed anticancer activity against many tumor cell lines, and had lower IC50 values than five other anticancer agents tested Liver tumors reduced more than 50% after 6 months in human subjects 15, 56, 57... 

Fang, J., Sawa, T., and Maeda, H. Factors and mechanism of EPR effect and the enhanced antitumor effects of macromolecular drugs including SMANCS. Adv. Exp. Med. Biol. 519 29-49. 2003. 

The cytotoxic neocarzinostatin (NCS) is a small protein (Mw 12 kD) associated with a low molecular weight chromophore. NCS is rapidly cleared by the kidney and its cytotoxicity is non-cell specific. To modify its disposition, two poly(styrene-co-maleic acid anhydride) copolymers (Mw 1,500) have been coupled to one molecule of NCS, to give styrene-maleic-anhydride-neocarcinostatin (SMANCS) systems. 

SMANCS has been shown to retain nearly all the in vitro activity of NCS, with much improved pharmacokinetic properties. Tumor uptake has been shown to increase in animal models, presumably by the EPR effect. Clinical successes have been reported with SMANCS in Lipiodol (a lymphographic vehicle) after intra-arterial administration in patients with unresectable hepatocellular carcinomas. 

SMANCS Neocarzinostatin Amide Clinically approved in Japan ... 

Maeda H, Sawa T, Konno T (2001) Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Release 74 47-61... 

Maeda H. SMANCS and polymer-conjugated macromolecular drugs advantages in cancer chemotherapy. Adv Drug Deliv Rev 1991 6 181-202. 

Koimo T, Maeda H. Targeting chemotherapy of hepatocellular carcinoma arterial administration of SMANCS/Lipiodol. In Okada K, Ishak KG, eds. Neoplasm in the Liver. New York Springer-Verlag, 1987 343. 

SMANCS Zinostatin, Stimalmer 1993 (Japan) Hepatocellular carcinoma 24... 

EU, European Union G-CSF, granulocyte colony-stimulating factor HGR, human growth hormone HIV, human immunodeficiency virus PEG, polyethylene glycol SCID, severe combined immunodeficiency SMANCS, styrene maleic anhydride TNF, tumor necrosis factor (modified from Ref. [22]). 

Fig. 34.3 Diagrammatic representation of the reaction between SMA and NCS to produce the conjugate SMANCS.

Another polyvinylic prodrug, SMANCS (Fig. 34.3), is a conjugate of a low molecular weight styrene maleic anhydride copolymer (SMA, 1.6 kDa) and neocarzinostatin (NCS). It is already marketed in Japan for the treatment of hepatocellular carcinoma. 

Hirayama, S., Sato, F., Oda, T. and Maeda, H. (1986) Stability of high molecular weight anticancer agent SMANCS and its transfer from oil-phase to water-phase. Jpn J. Antibiot. 39 815-822. 

Konno, T. and Maeda, H. (1987) Targeting chemotherapy of hepatocellular carcinoma arterial administration of smancs/lipiodol. In Okuda, K. and Ishak, K.G. (eds). Neoplasms of the Liver, pp. 343-352, chap. 27. Sptinger-Verlag, New York. 

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