Tags

Type your tag names separated by a space and hit enter

A mutated superantigen SEA D227A fusion diabody specific to MUC1 and CD3 in targeted cancer immunotherapy for bile duct carcinoma.
Cancer Immunol Immunother. 2002 Mar; 51(1):33-44.CI

Abstract

In cancer immunotherapy research, many bispecific antibodies (BsAbs) have been developed for directing T cells toward tumor cells. Recent advances in genetic engineering have made it possible to prepare immunoglobulin fragments consisting of variable domains using bacterial expression systems. Therefore, recombinant BsAbs, termed diabodies, have attracted particular attention. We have previously produced an anti-MUC1 x anti-CD3 diabody (Mx3 diabody) in an Escherichia coli (E. coli) expression system. In order to reinforce the antitumor effects of the Mx3 diabody, mutated superantigen staphylococcal enterotoxin A (SEA) D227A was genetically fused to the Mx3 diabody. The SEA D227A fusion Mx3 diabody (SEA D227A-Mx3 diabody) thus constructed showed remarkable MUC1-specific antitumor effects when used with effector cells (lymphokine-activated killer cells with T-cell phenotype [T-LAK] and peripheral blood mononuclear cells [PBMCs]). In the bile duct carcinoma (BDC)-xenografted severe combined immunodeficient (SCID) mouse model, it also demonstrated strong antitumor activity when administered i.v. together with T-LAK cells and interleukin-2 (IL-2). In this experiment, the complete disappearance of tumors was observed in 3 out of 6 mice, and the other 3 showed marked retardation of tumor growth. Therefore, the SEA D227A-Mx3 diabody is considered to be a promising reagent in specific targeted immunotherapy for BDC and other MUC1-positive carcinomas. This is the first report on a diabody that is effective in treating human solid cancers in the xenografted SCID mouse experimental model.

Authors+Show Affiliations

First Department of Surgery, Tohoku University School of Medicine, Sendai 980-8574, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11845258

Citation

Takemura, Shin-ichi, et al. "A Mutated Superantigen SEA D227A Fusion Diabody Specific to MUC1 and CD3 in Targeted Cancer Immunotherapy for Bile Duct Carcinoma." Cancer Immunology, Immunotherapy : CII, vol. 51, no. 1, 2002, pp. 33-44.
Takemura S, Kudo T, Asano R, et al. A mutated superantigen SEA D227A fusion diabody specific to MUC1 and CD3 in targeted cancer immunotherapy for bile duct carcinoma. Cancer Immunol Immunother. 2002;51(1):33-44.
Takemura, S., Kudo, T., Asano, R., Suzuki, M., Tsumoto, K., Sakurai, N., Katayose, Y., Kodama, H., Yoshida, H., Ebara, S., Saeki, H., Imai, K., Matsuno, S., & Kumagai, I. (2002). A mutated superantigen SEA D227A fusion diabody specific to MUC1 and CD3 in targeted cancer immunotherapy for bile duct carcinoma. Cancer Immunology, Immunotherapy : CII, 51(1), 33-44.
Takemura S, et al. A Mutated Superantigen SEA D227A Fusion Diabody Specific to MUC1 and CD3 in Targeted Cancer Immunotherapy for Bile Duct Carcinoma. Cancer Immunol Immunother. 2002;51(1):33-44. PubMed PMID: 11845258.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A mutated superantigen SEA D227A fusion diabody specific to MUC1 and CD3 in targeted cancer immunotherapy for bile duct carcinoma. AU - Takemura,Shin-ichi, AU - Kudo,Toshio, AU - Asano,Ryutaro, AU - Suzuki,Masanori, AU - Tsumoto,Kouhei, AU - Sakurai,Naoki, AU - Katayose,Yu, AU - Kodama,Hideaki, AU - Yoshida,Hiroshi, AU - Ebara,Shinji, AU - Saeki,Hisaaki, AU - Imai,Kohzoh, AU - Matsuno,Seiki, AU - Kumagai,Izumi, Y1 - 2002/01/11/ PY - 2001/08/30/received PY - 2001/10/18/accepted PY - 2002/2/15/pubmed PY - 2002/5/15/medline PY - 2002/2/15/entrez SP - 33 EP - 44 JF - Cancer immunology, immunotherapy : CII JO - Cancer Immunol Immunother VL - 51 IS - 1 N2 - In cancer immunotherapy research, many bispecific antibodies (BsAbs) have been developed for directing T cells toward tumor cells. Recent advances in genetic engineering have made it possible to prepare immunoglobulin fragments consisting of variable domains using bacterial expression systems. Therefore, recombinant BsAbs, termed diabodies, have attracted particular attention. We have previously produced an anti-MUC1 x anti-CD3 diabody (Mx3 diabody) in an Escherichia coli (E. coli) expression system. In order to reinforce the antitumor effects of the Mx3 diabody, mutated superantigen staphylococcal enterotoxin A (SEA) D227A was genetically fused to the Mx3 diabody. The SEA D227A fusion Mx3 diabody (SEA D227A-Mx3 diabody) thus constructed showed remarkable MUC1-specific antitumor effects when used with effector cells (lymphokine-activated killer cells with T-cell phenotype [T-LAK] and peripheral blood mononuclear cells [PBMCs]). In the bile duct carcinoma (BDC)-xenografted severe combined immunodeficient (SCID) mouse model, it also demonstrated strong antitumor activity when administered i.v. together with T-LAK cells and interleukin-2 (IL-2). In this experiment, the complete disappearance of tumors was observed in 3 out of 6 mice, and the other 3 showed marked retardation of tumor growth. Therefore, the SEA D227A-Mx3 diabody is considered to be a promising reagent in specific targeted immunotherapy for BDC and other MUC1-positive carcinomas. This is the first report on a diabody that is effective in treating human solid cancers in the xenografted SCID mouse experimental model. SN - 0340-7004 UR - https://www.unboundmedicine.com/medline/citation/11845258/A_mutated_superantigen_SEA_D227A_fusion_diabody_specific_to_MUC1_and_CD3_in_targeted_cancer_immunotherapy_for_bile_duct_carcinoma_ L2 - https://dx.doi.org/10.1007/s00262-001-0245-3 DB - PRIME DP - Unbound Medicine ER -