BIOMAT Database Logo BIOMAT Database Logo

Differential sensitivity of CD30+ neoplastic cells to gelonin delivered by anti-CD30/anti-gelonin bispecific antibodies. 1995

S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.

Lymphocyte activation antigens, such as CD30, represent suitable target molecules for antibody-driven drug delivery in haemopoietic malignancies. A ribosome-inactivating protein (RIP) type 1 of potential interest for mAb targeting is gelonin, which displays a lower toxicity, as compared to other RIPs. In this study, two anti-CD30/antigelonin bispecific monoclonal antibodies (bimAbs), secreted by hybrid hybridomas, were used to deliver this RIP to CD30+ tumour cells. The two bimAbs, termed D4 and A18, were produced using the same anti-CD30 mAb and two anti-gelonin mAbs, directed to unrelated epitopes of the gelonin molecule. These bimAbs enhanced gelonin toxicity (IC50 5 x 10(-8) M, in the absence of mAbs) against the CD30+ L540 Hodgkin's lymphoma cell line in a protein synthesis inhibition assay. Thus, in the presence of 10(-9) M D4 bimAb, protein synthesis was inhibited with an IC50 of 5 x 10(-10) M as gelonin, whereas with A18 bimAb the IC50 was 8 x 10(-11) M. More interestingly, the combined use of the two bimAbs had a synergistic effect, since the IC50 of gelonin reached 6 x 10(-12) M. Among CD30 tumour cell lines, the Hodgkin's lymphoma L428 was also sensitive to gelonin delivered by bimAbs (IC50 6 x 10(-11) M), whereas the COLE Hodgkin's cell line and the T-ALL Jurkat were completely resistant to the toxic effect of gelonin and bimAbs. COLE and Jurkat cells were also resistant to a gelonin/anti-CD30 conventional immunotoxin, whereas they were sensitive to a saporin/anti-CD30 immunotoxin. This suggests that the resistance to gelonin is not related to a lack of internalization through the CD30 molecule but is associated with some property of the RIP.

UI MeSH Term Description Entries
D010940 Plant Proteins Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which PLANT PROTEINS, DIETARY is available. Plant Protein,Protein, Plant,Proteins, Plant
D003602 Cytotoxicity, Immunologic The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement. Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D004306 Dose-Response Relationship, Immunologic A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell. Immunologic Dose-Response Relationship,Relationship, Immunologic Dose-Response,Dose Response Relationship, Immunologic,Dose-Response Relationships, Immunologic,Immunologic Dose Response Relationship,Immunologic Dose-Response Relationships,Relationship, Immunologic Dose Response,Relationships, Immunologic Dose-Response
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D006689 Hodgkin Disease A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen. Granuloma, Hodgkin,Granuloma, Malignant,Hodgkin Lymphoma,Lymphogranuloma, Malignant,Granuloma, Hodgkin's,Granuloma, Hodgkins,Hodgkin Lymphoma, Adult,Hodgkin's Disease,Hodgkin's Lymphoma,Hodgkins Disease,Lymphocyte Depletion Hodgkin's Lymphoma,Lymphocyte-Rich Classical Hodgkin's Lymphoma,Mixed Cellularity Hodgkin's Lymphoma,Nodular Lymphocyte-Predominant Hodgkin's Lymphoma,Nodular Sclerosing Hodgkin's Lymphoma,Adult Hodgkin Lymphoma,Disease, Hodgkin,Disease, Hodgkin's,Disease, Hodgkins,Hodgkin Granuloma,Hodgkin's Granuloma,Hodgkins Granuloma,Hodgkins Lymphoma,Lymphocyte Rich Classical Hodgkin's Lymphoma,Lymphogranulomas, Malignant,Lymphoma, Hodgkin,Lymphoma, Hodgkin's,Malignant Granuloma,Malignant Granulomas,Malignant Lymphogranuloma,Malignant Lymphogranulomas,Nodular Lymphocyte Predominant Hodgkin's Lymphoma
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000922 Immunotoxins Semisynthetic conjugates of various toxic molecules, including RADIOACTIVE ISOTOPES and bacterial or plant toxins, with specific immune substances such as IMMUNOGLOBULINS; MONOCLONAL ANTIBODIES; and ANTIGENS. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. Affinotoxin,Antibody-Toxin Conjugate,Antibody-Toxin Conjugates,Antibody-Toxin Hybrid,Antibody-Toxin Hybrids,Chimeric Toxins,Cytotoxin-Antibody Conjugate,Cytotoxin-Antibody Conjugates,Monoclonal Antibody-Toxin Conjugate,Targeted Toxin,Targeted Toxins,Toxin Carriers,Toxin Conjugates,Toxin-Antibody Conjugate,Toxin-Antibody Conjugates,Toxin-Antibody Hybrid,Toxin-Antibody Hybrids,Toxins, Chimeric,Toxins, Targeted,Affinotoxins,Chimeric Toxin,Immunotoxin,Monoclonal Antibody-Toxin Conjugates,Toxin Carrier,Toxin Conjugate,Antibody Toxin Conjugate,Antibody Toxin Conjugates,Antibody Toxin Hybrid,Antibody Toxin Hybrids,Antibody-Toxin Conjugate, Monoclonal,Antibody-Toxin Conjugates, Monoclonal,Carrier, Toxin,Carriers, Toxin,Conjugate, Antibody-Toxin,Conjugate, Cytotoxin-Antibody,Conjugate, Monoclonal Antibody-Toxin,Conjugate, Toxin,Conjugate, Toxin-Antibody,Conjugates, Antibody-Toxin,Conjugates, Cytotoxin-Antibody,Conjugates, Monoclonal Antibody-Toxin,Conjugates, Toxin,Conjugates, Toxin-Antibody,Cytotoxin Antibody Conjugate,Cytotoxin Antibody Conjugates,Hybrid, Antibody-Toxin,Hybrid, Toxin-Antibody,Hybrids, Antibody-Toxin,Hybrids, Toxin-Antibody,Monoclonal Antibody Toxin Conjugate,Monoclonal Antibody Toxin Conjugates,Toxin Antibody Conjugate,Toxin Antibody Conjugates,Toxin Antibody Hybrid,Toxin Antibody Hybrids,Toxin, Chimeric,Toxin, Targeted
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D017730 Ki-1 Antigen A member of the tumor necrosis factor receptor superfamily that may play a role in the regulation of NF-KAPPA B and APOPTOSIS. It is found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; NEUTROPHILS; EOSINOPHILS; MAST CELLS and NK CELLS. Overexpression of the Ki-1 antigen in hematopoietic malignancies make it clinically useful as a biological tumor marker. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS. Antigens, CD30,Antigens, Ki-1,Ber-H2 Antigens,CD30 Antigens,Ki-1 Antigens,Tumor Necrosis Factor Receptor Superfamily, Member 8,Ber-H2 Antigen,CD30 Antigen,TNFRSF8 Receptor,Antigen, Ber-H2,Antigen, CD30,Antigen, Ki-1,Antigens, Ber-H2,Antigens, Ki 1,Ber H2 Antigen,Ber H2 Antigens,Ki 1 Antigen,Ki 1 Antigens,Receptor, TNFRSF8
D054789 Ribosome Inactivating Proteins, Type 1 Ribosome inactivating proteins consisting of only the toxic A subunit, which is a polypeptide of around 30 kDa.

Related Publications

S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Targeting of saporin to Hodgkin's lymphoma cells by anti-CD30 and anti-CD25 bispecific antibodies.
September 1998, British journal of haematology,
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Novel anti-CD30/CD3 bispecific antibodies activate human T cells and mediate potent anti-tumor activity.
January 2023, Frontiers in immunology,
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Anti-CD16/CD30 bispecific antibodies as possible treatment for refractory Hodgkin's disease.
October 1998, Leukemia & lymphoma,
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Delivery of the ribosome-inactivating protein, gelonin, to lymphoma cells via CD22 and CD38 using bispecific antibodies.
May 1995, British journal of cancer,
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
CD30 in normal and neoplastic cells.
February 1999, Clinical immunology (Orlando, Fla.),
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Anti-CD30 Antibodies for Hodgkin lymphoma.
July 2010, Current hematologic malignancy reports,
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Specific activation of the prodrug mitomycin phosphate by a bispecific anti-CD30/anti-alkaline phosphatase monoclonal antibody.
November 1990, Cancer research,
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody.
March 1997, Blood,
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
Treatment of refractory Hodgkin's disease with an anti-CD16/CD30 bispecific antibody.
January 1997, Cancer immunology, immunotherapy : CII,
S Sforzini, and A Bolognesi, and R Meazza, and S Marciano, and P Casalini, and H Dürkop, and P L Tazzari, and H Stein, and F Stirpe, and S Ferrini
A novel tetravalent bispecific TandAb (CD30/CD16A) efficiently recruits NK cells for the lysis of CD30+ tumor cells.
January 2014, mAbs,
Copied contents to your clipboard!