Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents

Inna Gladysheva, N. A. Moroz, T. A. Karmakova, E. R. Nemtsova, R. I. Yakubovskaya, N. I. Larionova

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co-immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredients in the conjugate was the following BBI:D:sIgG=9:1:1. Comparison of the dose response curves for the native sIgG and the BBI-D-sIgG conjugate indicated that sIgG completely retained its specific activity (>90%) after modification with dextran. The determination of the Ki values for chymotrypsin interaction with the native BBI and the BBI-D-sIgG conjugate indicated high anti-chymotrypsin activity. In the next step, the monoclonal antibody (ICO 25 MAb) against the mucin-like human epithelial membrane antigen was used for conjugation as it is the most universal vector for targeting different agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The conjugated MAb reacted with tumor cells of different epithelial genesis (breast, lung, gastric, ovarian and uterus tumors), but did not react with tumor cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjugate has almost the same immunohistochemical activity as non-conjugated MAb. These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting.

Original languageEnglish (US)
Pages (from-to)303-316
Number of pages14
JournalJournal of Drug Targeting
Volume9
Issue number5
DOIs
StatePublished - Jan 1 2001

Fingerprint

Immunoconjugates
Protease Inhibitors
Soybeans
Antineoplastic Agents
Chymotrypsin
Dextrans
Neoplasms
Epithelial Cells
Anticarcinogenic Agents
Mucin-1
Antibodies
Mucins
Immobilization
Uterus
Immunoglobulin M
Immunoglobulins
Sheep
Stomach
Breast
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Gladysheva, I., Moroz, N. A., Karmakova, T. A., Nemtsova, E. R., Yakubovskaya, R. I., & Larionova, N. I. (2001). Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents. Journal of Drug Targeting, 9(5), 303-316. https://doi.org/10.3109/10611860108998767

Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents. / Gladysheva, Inna; Moroz, N. A.; Karmakova, T. A.; Nemtsova, E. R.; Yakubovskaya, R. I.; Larionova, N. I.

In: Journal of Drug Targeting, Vol. 9, No. 5, 01.01.2001, p. 303-316.

Research output: Contribution to journalArticle

Gladysheva, I, Moroz, NA, Karmakova, TA, Nemtsova, ER, Yakubovskaya, RI & Larionova, NI 2001, 'Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents', Journal of Drug Targeting, vol. 9, no. 5, pp. 303-316. https://doi.org/10.3109/10611860108998767
Gladysheva I, Moroz NA, Karmakova TA, Nemtsova ER, Yakubovskaya RI, Larionova NI. Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents. Journal of Drug Targeting. 2001 Jan 1;9(5):303-316. https://doi.org/10.3109/10611860108998767
Gladysheva, Inna ; Moroz, N. A. ; Karmakova, T. A. ; Nemtsova, E. R. ; Yakubovskaya, R. I. ; Larionova, N. I. / Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents. In: Journal of Drug Targeting. 2001 ; Vol. 9, No. 5. pp. 303-316.
@article{65a8a23904f6405b9c4e392c1aa8c508,
title = "Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents",
abstract = "To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co-immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredients in the conjugate was the following BBI:D:sIgG=9:1:1. Comparison of the dose response curves for the native sIgG and the BBI-D-sIgG conjugate indicated that sIgG completely retained its specific activity (>90{\%}) after modification with dextran. The determination of the Ki values for chymotrypsin interaction with the native BBI and the BBI-D-sIgG conjugate indicated high anti-chymotrypsin activity. In the next step, the monoclonal antibody (ICO 25 MAb) against the mucin-like human epithelial membrane antigen was used for conjugation as it is the most universal vector for targeting different agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The conjugated MAb reacted with tumor cells of different epithelial genesis (breast, lung, gastric, ovarian and uterus tumors), but did not react with tumor cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjugate has almost the same immunohistochemical activity as non-conjugated MAb. These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting.",
author = "Inna Gladysheva and Moroz, {N. A.} and Karmakova, {T. A.} and Nemtsova, {E. R.} and Yakubovskaya, {R. I.} and Larionova, {N. I.}",
year = "2001",
month = "1",
day = "1",
doi = "10.3109/10611860108998767",
language = "English (US)",
volume = "9",
pages = "303--316",
journal = "Journal of Drug Targeting",
issn = "1061-186X",
publisher = "Informa Healthcare",
number = "5",

}

TY - JOUR

T1 - Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents

AU - Gladysheva, Inna

AU - Moroz, N. A.

AU - Karmakova, T. A.

AU - Nemtsova, E. R.

AU - Yakubovskaya, R. I.

AU - Larionova, N. I.

PY - 2001/1/1

Y1 - 2001/1/1

N2 - To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co-immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredients in the conjugate was the following BBI:D:sIgG=9:1:1. Comparison of the dose response curves for the native sIgG and the BBI-D-sIgG conjugate indicated that sIgG completely retained its specific activity (>90%) after modification with dextran. The determination of the Ki values for chymotrypsin interaction with the native BBI and the BBI-D-sIgG conjugate indicated high anti-chymotrypsin activity. In the next step, the monoclonal antibody (ICO 25 MAb) against the mucin-like human epithelial membrane antigen was used for conjugation as it is the most universal vector for targeting different agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The conjugated MAb reacted with tumor cells of different epithelial genesis (breast, lung, gastric, ovarian and uterus tumors), but did not react with tumor cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjugate has almost the same immunohistochemical activity as non-conjugated MAb. These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting.

AB - To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co-immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis. The molar ratio of the ingredients in the conjugate was the following BBI:D:sIgG=9:1:1. Comparison of the dose response curves for the native sIgG and the BBI-D-sIgG conjugate indicated that sIgG completely retained its specific activity (>90%) after modification with dextran. The determination of the Ki values for chymotrypsin interaction with the native BBI and the BBI-D-sIgG conjugate indicated high anti-chymotrypsin activity. In the next step, the monoclonal antibody (ICO 25 MAb) against the mucin-like human epithelial membrane antigen was used for conjugation as it is the most universal vector for targeting different agents to human tumors of epithelial origin. The influence of conjugation on the specificity of the Mab reaction with its antigen was studied. The conjugated MAb reacted with tumor cells of different epithelial genesis (breast, lung, gastric, ovarian and uterus tumors), but did not react with tumor cells of non-epithelial origin. It was shown that BBI-D-ICO 25 MAb conjugate has almost the same immunohistochemical activity as non-conjugated MAb. These results demonstrated the feasibility of exploiting the activities of covalently bound BBI and ICO 25 MAb for anticarcinogenic agent targeting.

UR - http://www.scopus.com/inward/record.url?scp=0035178061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035178061&partnerID=8YFLogxK

U2 - 10.3109/10611860108998767

DO - 10.3109/10611860108998767

M3 - Article

VL - 9

SP - 303

EP - 316

JO - Journal of Drug Targeting

JF - Journal of Drug Targeting

SN - 1061-186X

IS - 5

ER -