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Patent · US4676980A · A · US

Target specific cross-linked heteroantibodies

(11) Publication number
US4676980A
(21) Application number
06/778,670
(22) Filing date
1985-09-23
(30) Priority date
1985-09-23
(43) Publication date
1987-06-30
(45) Date of grant
1987-06-30
(51) IPC
C07K 16/46
(52) CPC
  • C07K Peptides: 16/468, 2317/732
  • Y10S Technical subjects covered by former uspc cross-reference art collections [xracs] and digests: 436/819
(73) Assignee
US Department of Health and Human Services
(72) Inventors
David M. Segal; Pilar Perez
(54) Title
Target specific cross-linked heteroantibodies
(57) Abstract

The present invention discloses a target specific cross-linked heteroantibody and a method of producing the same. The cross-linked heteroantibodies of the present invention can cause normal autologous cells of the immune system to destroy any unwanted cell for which an antibody is available. Treatment or control of tumors, viral infected cells, fungi, bacteria, parasites and the like is now made possible through the use of the heteroantibody complex of the present invention.

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Claims (6)

  1. Cross-linked antibody heteroaggregates wherein one antibody of the heteroaggregate binds specifically with a receptor entity on a cytotoxic cell and a second antibody of the heteroaggregate binds specifically with a surface entity on a cell different from and to be lysed by the cytotoxic cell.
  2. The antibody heteroaggregate of claim 1 wherein said cytotoxic cell is selected from the group consisting of antibody-dependent cytolytic cell and cytotoxic T lymphocytes.
  3. The antibody heteroaggregate of claim 2, wherein the antibodies are cross-linked by avidin coupled to one antibody and biotin coupled to the second antibody.
  4. A method of destroying target cells in a mammalian host comprising administering to said host cytolytic amount of cross-linked heteroantibodies.
  5. A method of producing target specific heteroantibodies comprising cross-linking a first antibody directed against a receptor entity on a cytotoxic cell with a second antibody directed against a surface component of a target cell.
  6. The method according to claim 5 of cross-linking the first antibody to the second by coupling one antibody with avidin and the second antibody with biotin.

Description

1. Technical Field

The present invention is related generally to the field of immunochemistry. More particularly, the present invention is related to antibody heteroaggregates which cause normal cytotoxic cells to attack specifically targeted cell types.

2. State of the Art

The most widely used methods for eliminating pathogenic or otherwise undesired cells is through the use of drugs. In most cases, however, drugs are not totally specific for the target, and serious side effects result. This is especially true for anti-cancer agents which are highly toxic for normal cells and produce severe adverse reactions. Moreover many types of neoplasms are unresponsive to chemotherapy. Similarly anti-viral or immunosuppresive drugs also often exhibit many side effects.

One of the methods for obtaining increased specificity is through the use of target-specific antibodies, especially monoclonal antibodies. Such antibodies can, through their antibody binding sites, bind specifically to a designated target cell, for example a virally-infected cell, a tumor cell, a parasite, or a particular type of normal cell which expresses a distinctive cell surface antigen. However, the mere binding of antibodies to cells does not always lead to their destruction. Therefore, attempts have been made to render the antibodies cytotoxic by attaching a drug, toxin or radiolabelled isotope to them. Such "magic bullets", are under intense investigation. However, in many cases the antibody conjugates do not reach the target tissue because they are cleared rapidly from the circulation.

Citations (3)

  • US4048298A
  • US4433059A
  • US4490473A
Record as JSON
{
  "publication_number": "US4676980A",
  "country": "US",
  "kind": "A",
  "title": "Target specific cross-linked heteroantibodies",
  "abstract": "The present invention discloses a target specific cross-linked heteroantibody and a method of producing the same. The cross-linked heteroantibodies of the present invention can cause normal autologous cells of the immune system to destroy any unwanted cell for which an antibody is available. Treatment or control of tumors, viral infected cells, fungi, bacteria, parasites and the like is now made possible through the use of the heteroantibody complex of the present invention.",
  "claims": [
    "1. Cross-linked antibody heteroaggregates wherein one antibody of the heteroaggregate binds specifically with a receptor entity on a cytotoxic cell and a second antibody of the heteroaggregate binds specifically with a surface entity on a cell different from and to be lysed by the cytotoxic cell.",
    "2. The antibody heteroaggregate of claim 1 wherein said cytotoxic cell is selected from the group consisting of antibody-dependent cytolytic cell and cytotoxic T lymphocytes.",
    "3. The antibody heteroaggregate of claim 2, wherein the antibodies are cross-linked by avidin coupled to one antibody and biotin coupled to the second antibody.",
    "4. A method of destroying target cells in a mammalian host comprising administering to said host cytolytic amount of cross-linked heteroantibodies.",
    "5. A method of producing target specific heteroantibodies comprising cross-linking a first antibody directed against a receptor entity on a cytotoxic cell with a second antibody directed against a surface component of a target cell.",
    "6. The method according to claim 5 of cross-linking the first antibody to the second by coupling one antibody with avidin and the second antibody with biotin."
  ],
  "description_excerpt": "1. Technical Field\n\nThe present invention is related generally to the field of immunochemistry. More particularly, the present invention is related to antibody heteroaggregates which cause normal cytotoxic cells to attack specifically targeted cell types.\n\n2. State of the Art\n\nThe most widely used methods for eliminating pathogenic or otherwise undesired cells is through the use of drugs. In most cases, however, drugs are not totally specific for the target, and serious side effects result. This is especially true for anti-cancer agents which are highly toxic for normal cells and produce severe adverse reactions. Moreover many types of neoplasms are unresponsive to chemotherapy. Similarly anti-viral or immunosuppresive drugs also often exhibit many side effects.\n\nOne of the methods for obtaining increased specificity is through the use of target-specific antibodies, especially monoclonal antibodies. Such antibodies can, through their antibody binding sites, bind specifically to a designated target cell, for example a virally-infected cell, a tumor cell, a parasite, or a particular type of normal cell which expresses a distinctive cell surface antigen. However, the mere binding of antibodies to cells does not always lead to their destruction. Therefore, attempts have been made to render the antibodies cytotoxic by attaching a drug, toxin or radiolabelled isotope to them. Such \"magic bullets\", are under intense investigation. However, in many cases the antibody conjugates do not reach the target tissue because they are cleared rapidly from the circulation.",
  "cpc": [
    "C07K 16/468",
    "C07K 2317/732",
    "Y10S 436/819"
  ],
  "ipc": [
    "C07K 16/46"
  ],
  "assignees": [
    "US Department of Health and Human Services"
  ],
  "inventors": [
    "David M. Segal",
    "Pilar Perez"
  ],
  "filing_date": "1985-09-23",
  "publication_date": "1987-06-30",
  "grant_date": "1987-06-30",
  "priority_date": "1985-09-23",
  "application_number": "US-77867085-A",
  "family_id": "25114087",
  "cited_by_count": 3441,
  "citations": [
    "US4048298A",
    "US4433059A",
    "US4490473A"
  ]
}

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