The use of antifibrin antibodies for the destruction of tumor cells

Lee, F. H.; Fujimoto, Shigeyoshi; Sehon, A.H.

doi:10.1007/bf00199627

Cited by 7 publications

(2 citation statements)

References 26 publications

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“…Many investigators have described this incomplete clearance from the liver (intact antibody) or kidneys (antibody fragments) when luIn-DTPA-conjugated Ab was used (23)(24)(25)(26). Other approaches to radiolabeling antibodies which used functionalized DTPA or EDTA (ethylenediaminetetraacetic acid) to covalently attach the chelate to the antibody have been utilized with similar results (13)(14)(15)(27)(28)(29)(30)(31)(32).…”

Section: Acknowledgmentmentioning

confidence: 99%

“…The methods used for linking daunomycin to macromolecules have involved (a) cleavage of the bond between C-3 and C-4 of daunosamine producing carbonyl groups capable of reacting with the free amino groups of the protein (3,5,7,10,23,27), (b) reaction at the amino group of the amino-sugar moiety (17,24) using the crosslinking agents glutaraldehyde (8,9,19,27,28), carbodiimide (9, 25, 27), SPDP (21), and MBS (4), or (c) attachment to the methyl ketone side chain of the aglycon by nucleophilic substitution on its 14-bromo derivatives (6,16,21). Attachment of daunomycin was also achieved by the introduction of a peptidyl (11,12,18), maleyl (14), succinyl (15), or acid-labile cis-aconityl (13,14,21,29) spacer.…”

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Immunoconjugate design: a predictive approach for coupling of daunomycin to monoclonal antibodies

Hudecz¹,

Ross²,

Price³

et al. 1990

Bioconjugate Chem.

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There is increasing interest in the development of daunomycin-antibody immunoconjugates for the targeting of drug to specific cells or tissues. To this end, we have examined the factors influencing the synthesis of daunomycin-monoclonal antibody conjugates linked covalently by an acid-labile cis-aconitic spacer (which is considered to aid drug release from immunoconjugates in the lysosomes and thus enhance their cytotoxic potential). A rapid and efficient procedure for the purification of drug from contaminants and stabilizers was first developed; conditions for the optimal preparation of cis-aconityldaunomycin were established; products were analyzed and identified by TLC and HPLC. The coupling of cis-aconityldaunomycin to antibody was accomplished by activating the modified drug with a carbodiimide before addition to antibody. Several factors were identified which influenced the efficiency of the conjugation; in particular, the compositional features of the antibody which determine its electrophoretic charge characteristics were of profound effect. However, by appropriate choice and control of buffer pH during conjugation, it was possible to define conditions resulting in the controlled substitution of antibody with drug. The consequent effects upon the cell-binding activity of immunoconjugates were established and related to the extent of substitution. The procedures described enable appropriate reaction conditions to be selected for the linkage of daunomycin to antibody (at set drug/antibody molar ratios) and in good yield, based upon consideration of the compositional and charge properties of the antibody.

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Section: Acknowledgmentmentioning

confidence: 99%

mentioning

confidence: 99%

Immunoconjugate design: a predictive approach for coupling of daunomycin to monoclonal antibodies

Hudecz¹,

Ross²,

Price³

et al. 1990

Bioconjugate Chem.

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Relationship of tumor leucocytic infiltration to host defense mechanisms and prognosis

1984

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The interface between the tumor and the host is often the site of leucocytic infiltration. We will examine the idea that the infiltrating leucocytes of human and experimental tumors are components of the host immunological defense against the tumor, and that the presence of the infiltrate is a marker of favorable prognosis. Leucocytes could infiltrate tumors because of an active immune response, either nonspecific or specifically directed to tumor-associated antigens. Leucocyte influx may also occur because of chemotactic factors secreted by the tumor cells. Some tumors release factors which enhance vascular permeability and permit improved access by leucocytes to the tumor focus. The consequences of leucocytic infiltration include tumor cell cytolysis, cytostasis, or stimulation of proliferation. The present state of our knowledge of the interactions between tumor cells and infiltrating leucocytes precludes broad generalization of mechanisms. Further study will probably reveal that the mechanisms are diverse, and that there are some systems in which immune interactions occur at this interface and others in which they do not.

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