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MUC1-specific targeting immunotherapy with bispecific antibodies: inhibition of xenografted human bile duct carcinoma growth.
Cancer Res. 1996 Sep 15; 56(18):4205-12.CR

Abstract

For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we synthesized two bispecific antibodies (BsAbs), MUC1 x CD3 BsAb constructed with MUSE11 (anti-MUC1 tumor antigen) and OKT-3 (anti-CD3), and MUC1 x CD28 BsAb constructed with MUSE11 and 15E8 (anti-CD28) antibodies. These two BsAbs reacted well with both MUC1-positive target tumor cells and effector lymphokine-activated killer (LAK) cells. Investigation of in vitro cytotoxicity [3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide assay] revealed that the MUC1 x CD3 BsAb could antigen-specifically enhance the cytotoxicity of LAK cells. Addition of the two BsAbs (MUC1 x CD3 BsAb plus MUC1 x CD28 BsAb) in vitro resulted in a 60% cytotoxicity, similar to that obtained with BsAb (MUC1 x CD3) alone. Interleukin 12-induced LAK cells demonstrated far greater cytotoxicity (50%) than their interleukin 2-induced counterparts (LAK cells), and this was also enhanced by the BsAbs. When 2 x 10(7) LAK cells sensitized with both kinds of BsAbs were administered four times i.v. to BDC-grafted severe combined immunodeficient mice (tumor size 5 mm in diameter), inhibition of tumor growth was observed. Thus, BsAb-LAK therapy for control of BDC warrants clinical trials.

Authors+Show Affiliations

First Department of Surgery, Tohoku University School of Medicine, Sendai, 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 available

Pub Type(s)

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

Language

eng

PubMed ID

8797593

Citation

Katayose, Y, et al. "MUC1-specific Targeting Immunotherapy With Bispecific Antibodies: Inhibition of Xenografted Human Bile Duct Carcinoma Growth." Cancer Research, vol. 56, no. 18, 1996, pp. 4205-12.
Katayose Y, Kudo T, Suzuki M, et al. MUC1-specific targeting immunotherapy with bispecific antibodies: inhibition of xenografted human bile duct carcinoma growth. Cancer Res. 1996;56(18):4205-12.
Katayose, Y., Kudo, T., Suzuki, M., Shinoda, M., Saijyo, S., Sakurai, N., Saeki, H., Fukuhara, K., Imai, K., & Matsuno, S. (1996). MUC1-specific targeting immunotherapy with bispecific antibodies: inhibition of xenografted human bile duct carcinoma growth. Cancer Research, 56(18), 4205-12.
Katayose Y, et al. MUC1-specific Targeting Immunotherapy With Bispecific Antibodies: Inhibition of Xenografted Human Bile Duct Carcinoma Growth. Cancer Res. 1996 Sep 15;56(18):4205-12. PubMed PMID: 8797593.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MUC1-specific targeting immunotherapy with bispecific antibodies: inhibition of xenografted human bile duct carcinoma growth. AU - Katayose,Y, AU - Kudo,T, AU - Suzuki,M, AU - Shinoda,M, AU - Saijyo,S, AU - Sakurai,N, AU - Saeki,H, AU - Fukuhara,K, AU - Imai,K, AU - Matsuno,S, PY - 1996/9/15/pubmed PY - 1996/9/15/medline PY - 1996/9/15/entrez SP - 4205 EP - 12 JF - Cancer research JO - Cancer Res VL - 56 IS - 18 N2 - For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we synthesized two bispecific antibodies (BsAbs), MUC1 x CD3 BsAb constructed with MUSE11 (anti-MUC1 tumor antigen) and OKT-3 (anti-CD3), and MUC1 x CD28 BsAb constructed with MUSE11 and 15E8 (anti-CD28) antibodies. These two BsAbs reacted well with both MUC1-positive target tumor cells and effector lymphokine-activated killer (LAK) cells. Investigation of in vitro cytotoxicity [3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide assay] revealed that the MUC1 x CD3 BsAb could antigen-specifically enhance the cytotoxicity of LAK cells. Addition of the two BsAbs (MUC1 x CD3 BsAb plus MUC1 x CD28 BsAb) in vitro resulted in a 60% cytotoxicity, similar to that obtained with BsAb (MUC1 x CD3) alone. Interleukin 12-induced LAK cells demonstrated far greater cytotoxicity (50%) than their interleukin 2-induced counterparts (LAK cells), and this was also enhanced by the BsAbs. When 2 x 10(7) LAK cells sensitized with both kinds of BsAbs were administered four times i.v. to BDC-grafted severe combined immunodeficient mice (tumor size 5 mm in diameter), inhibition of tumor growth was observed. Thus, BsAb-LAK therapy for control of BDC warrants clinical trials. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/8797593/MUC1_specific_targeting_immunotherapy_with_bispecific_antibodies:_inhibition_of_xenografted_human_bile_duct_carcinoma_growth_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=8797593 DB - PRIME DP - Unbound Medicine ER -