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Delivery of saporin to human B-cell lymphoma using bispecific antibody: targeting via CD22 but not CD19, CD37, or immunoglobulin results in efficient killing.
Cancer Res. 1993 Jul 01; 53(13):3015-21.CR

Abstract

A panel of bispecific F(ab')2 antibodies (BsAb) have been constructed for delivering the ribosome-inactivating protein saporin to human B cell lymphoma. Each derivative was prepared with specificity for saporin and CD19, CD22, CD37, or immunoglobulin. In vitro studies measuring inhibition of [3H]leucine uptake by cultured Daudi and Raji cells demonstrated that, despite all BsAb capturing saporin on the cell surface, BsAb targeting through CD22 were far more cytotoxic than those functioning via CD19, CD37, or surface immunoglobulin. This exceptional activity of the CD22-specific BsAb appears to derive from its ability to deliver and accumulate saporin inside the target cells. Further studies showed that four CD22-specific BsAb all performed with equal potency and were able to increase saporin toxicity (50% inhibitory concentration) up to 1000-fold, from 2 x 10(-7) M to 2 x 10(-10) M. Pairs of anti-CD22 BsAb which recognized different nonblocking epitopes on the saporin molecule were able to bind saporin more avidly to the target cell and, as a consequence, increased cytotoxicity by at least an additional 10-fold, resulting in 50% inhibitory concentration for protein synthesis of 2 x 10(-11) M. These results suggest that selected combinations of BsAb which bind cooperatively to a toxin and the cell surface may provide an efficient way of delivering toxins to unwanted cells in patients.

Authors+Show Affiliations

Lymphoma Research Unit, Tenovus Laboratory, General Hospital, Southampton, United Kingdom.No 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

7686448

Citation

Bonardi, M A., et al. "Delivery of Saporin to Human B-cell Lymphoma Using Bispecific Antibody: Targeting Via CD22 but Not CD19, CD37, or Immunoglobulin Results in Efficient Killing." Cancer Research, vol. 53, no. 13, 1993, pp. 3015-21.
Bonardi MA, French RR, Amlot P, et al. Delivery of saporin to human B-cell lymphoma using bispecific antibody: targeting via CD22 but not CD19, CD37, or immunoglobulin results in efficient killing. Cancer Res. 1993;53(13):3015-21.
Bonardi, M. A., French, R. R., Amlot, P., Gromo, G., Modena, D., & Glennie, M. J. (1993). Delivery of saporin to human B-cell lymphoma using bispecific antibody: targeting via CD22 but not CD19, CD37, or immunoglobulin results in efficient killing. Cancer Research, 53(13), 3015-21.
Bonardi MA, et al. Delivery of Saporin to Human B-cell Lymphoma Using Bispecific Antibody: Targeting Via CD22 but Not CD19, CD37, or Immunoglobulin Results in Efficient Killing. Cancer Res. 1993 Jul 1;53(13):3015-21. PubMed PMID: 7686448.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delivery of saporin to human B-cell lymphoma using bispecific antibody: targeting via CD22 but not CD19, CD37, or immunoglobulin results in efficient killing. AU - Bonardi,M A, AU - French,R R, AU - Amlot,P, AU - Gromo,G, AU - Modena,D, AU - Glennie,M J, PY - 1993/7/1/pubmed PY - 1993/7/1/medline PY - 1993/7/1/entrez SP - 3015 EP - 21 JF - Cancer research JO - Cancer Res VL - 53 IS - 13 N2 - A panel of bispecific F(ab')2 antibodies (BsAb) have been constructed for delivering the ribosome-inactivating protein saporin to human B cell lymphoma. Each derivative was prepared with specificity for saporin and CD19, CD22, CD37, or immunoglobulin. In vitro studies measuring inhibition of [3H]leucine uptake by cultured Daudi and Raji cells demonstrated that, despite all BsAb capturing saporin on the cell surface, BsAb targeting through CD22 were far more cytotoxic than those functioning via CD19, CD37, or surface immunoglobulin. This exceptional activity of the CD22-specific BsAb appears to derive from its ability to deliver and accumulate saporin inside the target cells. Further studies showed that four CD22-specific BsAb all performed with equal potency and were able to increase saporin toxicity (50% inhibitory concentration) up to 1000-fold, from 2 x 10(-7) M to 2 x 10(-10) M. Pairs of anti-CD22 BsAb which recognized different nonblocking epitopes on the saporin molecule were able to bind saporin more avidly to the target cell and, as a consequence, increased cytotoxicity by at least an additional 10-fold, resulting in 50% inhibitory concentration for protein synthesis of 2 x 10(-11) M. These results suggest that selected combinations of BsAb which bind cooperatively to a toxin and the cell surface may provide an efficient way of delivering toxins to unwanted cells in patients. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/7686448/Delivery_of_saporin_to_human_B_cell_lymphoma_using_bispecific_antibody:_targeting_via_CD22_but_not_CD19_CD37_or_immunoglobulin_results_in_efficient_killing_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7686448 DB - PRIME DP - Unbound Medicine ER -