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Recombinant RFB4 immunotoxins exhibit potent cytotoxic activity for CD22-bearing cells and tumors.
Blood. 1997 Sep 01; 90(5):2020-6.Blood

Abstract

Many B-cell malignancies express the CD22 antigen on their cell surface. To kill cells expressing this antigen, the RFB4 monoclonal antibody (MoAb) has been linked chemically with either deglycosylated ricin A chain or truncated versions of Pseudomonas exotoxin. These immunotoxins exhibited selective cytotoxic activity for CD22+ cells and antitumor activity in nude mouse models bearing human B-cell lymphomas. To construct a recombinant immunotoxin targeted to CD22, we first cloned the variable portions of the heavy and light chains of RFB4. The cloned Fv fragments were joined by a newly created disulfide bond to form a disulfide stabilized (ds) construct. The RFB4 construct was combined by gene fusion with PE38, a truncated version of PE. The recombinant immunotoxin was then expressed in Escherichia coli, purified by column chromatography and tested for cytotoxicity activity. RFB4(dsFv)PE38 retained its binding activity for CD22, was very stable at 37 degrees C and exhibited selective cytotoxic activity for CD22+-cultured cell lines. Because of its favorable binding characteristics and potency for CD22-positive cell lines, RFB4(dsFv)PE38 was tested for antitumor activity in a nude mouse model of human lymphoma. CA46 cells were injected subcutaneously and then treated with the RFB4(dsFv)PE38 immunotoxin. Antitumor activity was dose responsive and was not evident when an irrelevant immunotoxin was administered on the same schedule.

Authors+Show Affiliations

Laboratory of Molecular Biology, DCBDC, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9292538

Citation

Mansfield, E, et al. "Recombinant RFB4 Immunotoxins Exhibit Potent Cytotoxic Activity for CD22-bearing Cells and Tumors." Blood, vol. 90, no. 5, 1997, pp. 2020-6.
Mansfield E, Amlot P, Pastan I, et al. Recombinant RFB4 immunotoxins exhibit potent cytotoxic activity for CD22-bearing cells and tumors. Blood. 1997;90(5):2020-6.
Mansfield, E., Amlot, P., Pastan, I., & FitzGerald, D. J. (1997). Recombinant RFB4 immunotoxins exhibit potent cytotoxic activity for CD22-bearing cells and tumors. Blood, 90(5), 2020-6.
Mansfield E, et al. Recombinant RFB4 Immunotoxins Exhibit Potent Cytotoxic Activity for CD22-bearing Cells and Tumors. Blood. 1997 Sep 1;90(5):2020-6. PubMed PMID: 9292538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombinant RFB4 immunotoxins exhibit potent cytotoxic activity for CD22-bearing cells and tumors. AU - Mansfield,E, AU - Amlot,P, AU - Pastan,I, AU - FitzGerald,D J, PY - 1997/9/18/pubmed PY - 1997/9/18/medline PY - 1997/9/18/entrez SP - 2020 EP - 6 JF - Blood JO - Blood VL - 90 IS - 5 N2 - Many B-cell malignancies express the CD22 antigen on their cell surface. To kill cells expressing this antigen, the RFB4 monoclonal antibody (MoAb) has been linked chemically with either deglycosylated ricin A chain or truncated versions of Pseudomonas exotoxin. These immunotoxins exhibited selective cytotoxic activity for CD22+ cells and antitumor activity in nude mouse models bearing human B-cell lymphomas. To construct a recombinant immunotoxin targeted to CD22, we first cloned the variable portions of the heavy and light chains of RFB4. The cloned Fv fragments were joined by a newly created disulfide bond to form a disulfide stabilized (ds) construct. The RFB4 construct was combined by gene fusion with PE38, a truncated version of PE. The recombinant immunotoxin was then expressed in Escherichia coli, purified by column chromatography and tested for cytotoxicity activity. RFB4(dsFv)PE38 retained its binding activity for CD22, was very stable at 37 degrees C and exhibited selective cytotoxic activity for CD22+-cultured cell lines. Because of its favorable binding characteristics and potency for CD22-positive cell lines, RFB4(dsFv)PE38 was tested for antitumor activity in a nude mouse model of human lymphoma. CA46 cells were injected subcutaneously and then treated with the RFB4(dsFv)PE38 immunotoxin. Antitumor activity was dose responsive and was not evident when an irrelevant immunotoxin was administered on the same schedule. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/9292538/Recombinant_RFB4_immunotoxins_exhibit_potent_cytotoxic_activity_for_CD22_bearing_cells_and_tumors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-4971(20)58812-5 DB - PRIME DP - Unbound Medicine ER -