Monoclonal Antibodies

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In the 1890s, German physician and bacteriologist Paul Erhlich coined the term “antibodies” to explain the substances found in blood serum which neutralized specific bacterial toxins. He recognized the potential of these unique molecules to act as “magic bullets” against disease. He envisioned drugs made from specific antibodies targeting only invading organisms or toxins while leaving the rest of the body unaffected.

The invention of monoclonal antibody (mAb) technology provided scientists with a tool to pursue that dream. In 1975, researchers César Milstein and Georges Köhler, working at the Laboratory for Molecular Biology in England, developed a technique for creating cells that could pump out streams of identical antibodies. Their invention built on years of scientific research on the immune system and cell culture (growing cells outside the body). It worked by merging two kinds of cells—cancerous human B cells and mouse spleen cells that had been induced to produce the desired antibody. These fused cells, called hybridomas, could be grown in culture. The identical antibodies they produced became known as monoclonal antibodies.

Previously, the antibodies for use in medicine and diagnostics were extracted from blood. Scientists exposed animals to the desired antigen (usually a bacteria, virus, or toxin), causing the body to produce antibodies. They then harvested blood from the animals and separated out the antibody-containing blood serum. However, due to variability in antibody production between individual animals, it was difficult to obtain consistent levels of antibodies in different batches of blood products. The blood also contained a variety of other antibodies, created by the animal’s immune system in reaction to everyday antigens. This made antibodies from serum sources variable in concentration and purity.

Anti-diphtheritic serums, 1898

Anti-diphtheritic serum, 1898

In contrast, mAb technology guaranteed a steady source of a single kind of antibody. The technique also eliminated the problem of variability of antibody concentration. Essentially, it allowed for a standardized product of known composition.

Antibodies have been used in diagnostics since the late 19th century. By 1985, ten years after Köhler and Milstein’s invention, the Food and Drug Administration (FDA) had approved more than 70 mAb-based diagnostic tests for use in the United States. By the late 1980s, one third of the approvals for mAb diagnostics were for pregnancy tests, which remain the most common at home diagnostic. Pregnancy tests use antibodies that bind to human chorionic gonadotrophin (hCG). The presence of this hormone in the urine indicates a woman is pregnant.

The QTest, a pregnancy test and ovulation predictor
The QTest, a pregnancy test and ovulation predictor
The QTest, a pregnancy test and ovulation predictor

mAbs were also used in ovulation prediction tests to help women either get pregnant or avoid pregnancy. The QTest by Beckton, Dickinson & Co. was available both as a pregnancy test and an ovulation predictor, seen in three views here.

The first mAb drug approved by the FDA was Orthoclone, in June 1986. The drug prevented kidney rejection in transplant patients. The mAb worked by binding to and disrupting the functioning of human T cells, which are largely responsible for organ rejection. However, Orthoclone provoked serious side effects, including allergic reactions to the mouse-cell derived antibodies.

Orthoclone OKT3
Simulect

Orthoclone OKT3 (left) and Simulect, another immunosuppressant mAb drug. Orthoclone sometimes triggered severe reactions because it utilized mouse-cell derived antibodies. Simulect, approved for use in 1998, used genetically engineered antibodies that were part mouse, part human, thereby reducing allergic reactions to the drug.

Orthoclone approval came only seven years after its discovery, a relatively quick turnaround. Nevertheless, it would take until the late 1990s for mAb drug approvals to really take off. Unlike diagnostics, therapeutics actually entered the human body, creating larger safety concerns. Drugs also required larger numbers of mAbs. Companies had to find a way to scale-up mAb production, which proved challenging.

Rituxan (rituximab) for injection

Rituxan (rituximab) for injection. Two biotech companies, Idec and Genentech, formed a partnership to develop and market the drug.

In 1997, a milestone in mAb therapeutics was achieved with the FDA approval of Rituxan, the first mAb for cancer treatment. Rituxin is used to treat cancers such as leukemias and lymphomas, which are characterized by production of abnormal white blood cells. Rituxin binds to receptors on these cells, which helps the body to destroy them.

Cancer treatment had long been a goal for mAbs. Researchers hoped the targeted therapies would mean fewer side effects. Traditional treatments like chemotherapy and radiation damage both healthy and cancerous cells. Since Rituxan’s approval, approximately half of mAb drugs on the market have targeted cancer.

Today, mAbs are approved to treat a wide range of diseases and disorders, from breast cancer to psoriasis.

 

Actimmune is a recombinant pharmaceutical used to treat children and adults with chronic granulomatous disease (CGD, an immune system disorder) and severe, malignant osteopetrosis (a disease which causes bones to become extremely dense and can lead to blindness, scoliosis, and a
Description (Brief)
Actimmune is a recombinant pharmaceutical used to treat children and adults with chronic granulomatous disease (CGD, an immune system disorder) and severe, malignant osteopetrosis (a disease which causes bones to become extremely dense and can lead to blindness, scoliosis, and a number of other problems).
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human interferon are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferon, which is harvested and used as the active ingredient in Actimmune.
Object is a plastic clamshell-style box with tabs for opening labeled "HOLD" and "LIFT." Box contains 12 single-dose vials, which are round, clear glass bottles with blue plastic tops and white labels with black and green printing.
Location
Currently not on view
date made
before November 1993
maker
Genentech, Inc.
ID Number
2012.0046.49
accession number
2012.0046
catalog number
2012.0046.49
(From box) For Intravenous Use(From insert)Metastatic Colorectal Cancer (mCRC) Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-flurouracil-based chemotherapy.Non-Squamous N
Description (Brief)
(From box) For Intravenous Use
(From insert)
Metastatic Colorectal Cancer (mCRC) Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-flurouracil-based chemotherapy.
Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer in combination with carboplatin and paclitaxel.
Glioblastoma Avastin is indicated for the treatment of glioblastoma with progressive disease in adult patients following prior therapy as a single agent. The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin.
Metastatic Renal Cell Carcinoma (mRCC) Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.
Location
Currently not on view
date made
ca 2013
product expiration date
2014-10
maker
Genentech, Inc.
ID Number
2013.0069.02
catalog number
2013.0069.02
accession number
2013.0069
maker number
510569
(From insert) Herceptin is a HER2/neu receptor antagonist indicated for:-the threatment of HER2 overexpressing breast cancer-the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinomaCurrently not on view
Description (Brief)
(From insert) Herceptin is a HER2/neu receptor antagonist indicated for:
-the threatment of HER2 overexpressing breast cancer
-the treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma
Location
Currently not on view
date made
ca 2013
product expiration date
2015-07
maker
Genentech, Inc.
ID Number
2013.0069.05
catalog number
2013.0069.05
accession number
2013.0069
(From insert) KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate indicated, as a single agent, for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.
Description (Brief)
(From insert) KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate indicated, as a single agent, for the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. Patients should have either:
--Received prior therapy for metastatic disease, or
-- Developed disease rescurrence during or within six months of completing adjuvant therapy.
Location
Currently not on view
date made
ca 2013
product expiration date
2015-11
maker
Genentech, Inc.
ID Number
2013.0069.06
catalog number
2013.0069.06
accession number
2013.0069
(From box) For intravitreal injection only.(From insert) LUCENTIS is indicated for the treatment of patients with:--NEovascular (Wet) Age-Related Macular Degeneration--Macular Edema Followign Retinal Vein Occlusion--Diabetic Macular EdemaCurrently not on view
Description (Brief)
(From box) For intravitreal injection only.
(From insert) LUCENTIS is indicated for the treatment of patients with:
--NEovascular (Wet) Age-Related Macular Degeneration
--Macular Edema Followign Retinal Vein Occlusion
--Diabetic Macular Edema
Location
Currently not on view
date made
ca 2013
product expiration date
2015-07
maker
Genentech, Inc.
ID Number
2013.0069.07
catalog number
2013.0069.07
accession number
2013.0069
(From box) Dilute prior to use; for intravenous infusion only; single-use vial; discard unused portion(From insert)PERJETA is a HER2/neu receptor antagonist indicated in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast
Description (Brief)
(From box) Dilute prior to use; for intravenous infusion only; single-use vial; discard unused portion
(From insert)
PERJETA is a HER2/neu receptor antagonist indicated in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
Location
Currently not on view
date made
ca 2013
product expiration date
2014-02
maker
Genentech, Inc.
ID Number
2013.0069.09
catalog number
2013.0069.09
accession number
2013.0069
(From box) For single-use IV administration only.(From insert)RITUXAN is a CD20-directed cytolytic antibody indicated for the treatment of patients with:--Non-Hodgkin's Lymphoma--Chronic Lymphocytic Leukemia--Rheumatoid Arthritis in combination with methotrexate in adult patients
Description (Brief)
(From box) For single-use IV administration only.
(From insert)
RITUXAN is a CD20-directed cytolytic antibody indicated for the treatment of patients with:
--Non-Hodgkin's Lymphoma
--Chronic Lymphocytic Leukemia
--Rheumatoid Arthritis in combination with methotrexate in adult patients with moderately-to severely-active RA who have inadequate response to one or more TNF antagonist therapies
-Wegener's Granulomatosis and Microscopic Polyangiitis in adult patients in combination with glucocorticoids
Location
Currently not on view
date made
ca 2013
product expiration date
2015-03
maker
Genentech, Inc.
ID Number
2013.0069.10
catalog number
2013.0069.10
accession number
2013.0069
(From box)For subcutaneous use(From insert)Xolair is indicated for:-Moderate to severe persistent asthma in patients with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids.Important L
Description (Brief)
(From box)
For subcutaneous use
(From insert)
Xolair is indicated for:
-Moderate to severe persistent asthma in patients with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids.
Important Limitations of use:
-Not indicated for other allergic conditions
-Not indicated for acute bronchospasm or status asthmaticus
-Not indicated for pediatric patients less than 12 years of age
Location
Currently not on view
date made
ca 2013
product expiration date
2016-08
maker
Genentech, Inc.
Novartis Vaccines and Diagnostics Limited
ID Number
2013.0069.13
catalog number
2013.0069.13
accession number
2013.0069
Orthoclone OKT3 prevents rejection of new tissues in patients who have received kidney grafts.
Description (Brief)
Orthoclone OKT3 prevents rejection of new tissues in patients who have received kidney grafts. It was the first drug created through monoclonal antibody technology to be approved for human use.
Monoclonal antibody technology uses specially made cells as tiny factories to pump out pure sources of a single antibody. Prior to its development, it was very difficult to isolate large amounts of a single antibody for therapeutic use.
Monoclonal antibody cells are created by fusing two cells of different origins. One cell, from a mouse's spleen, produces the antibody. The other cell, from a tumor, has the ability to replicate continuously. By fusing the two cells, a new cell is created which has the best characteristics of both-it produces the antibody and also grows quickly. These new cells produce large amounts of pure antibodies which are harvested for use in drugs like Orthoclone OKT3.
The object is a clear glass 5 mL ampule with a blue ring around the neck and a clear label with blue printing. It is housed in a formfitting plastic case with snap top and snap sides.
Location
Currently not on view
date made
ca 1986
maker
Ortho Pharmaceutical Corporation
ID Number
1987.0780.01
accession number
1987.0780
catalog number
1987.0780.01
Roferon-A is an injectible, recombinant pharmaceutical used to treat different types of leukemia, malignant melanoma, multiple myeloma, non-Hodgkin's lymphoma, AIDS-related sarcoma, and hepatitis.
Description (Brief)
Roferon-A is an injectible, recombinant pharmaceutical used to treat different types of leukemia, malignant melanoma, multiple myeloma, non-Hodgkin's lymphoma, AIDS-related sarcoma, and hepatitis. It was discontinued in October 2007, as new therapies for the diseases it treated were developed.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human interferon are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferon, which is harvested and used as the active ingredient in Roferon-A.
Object consists of a sealed white cardboard box with red and black printing. Box contains one multiple-dose vial.
Location
Currently not on view
product expiration date
1988-07-01
maker
Hoffmann-La Roche
Roche Laboratories
ID Number
1987.0786.01
accession number
1987.0786
catalog number
1987.0786.01
Roferon-A is an injectible, recombinant pharmaceutical used to treat different types of leukemia, malignant melanoma, multiple myeloma, non-Hodgkin's lymphoma, AIDS-related sarcoma, and hepatitis.
Description (Brief)
Roferon-A is an injectible, recombinant pharmaceutical used to treat different types of leukemia, malignant melanoma, multiple myeloma, non-Hodgkin's lymphoma, AIDS-related sarcoma, and hepatitis. It was discontinued in October 2007, as new therapies for the diseases it treated were developed.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human interferon are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferon, which is harvested and used as the active ingredient in Roferon-A.
Object consists of a sealed white cardboard box with red and black printing. Box contains 10 single-use, 1 mL vials.
Location
Currently not on view
date made
ca 1988
product expiration date
1988-04-01
maker
Hoffmann-La Roche
Roche Laboratories
ID Number
1987.0786.02
accession number
1987.0786
catalog number
1987.0786.02
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur.
Description (Brief)
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human white blood cell interferons are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferons, which are harvested and used as the active ingredient in Intron A.
Object consists of a cardboard box containing a second box, two glass bottles (one of the active pharmaceutical and one of the dilutent), and two product inserts.
Location
Currently not on view
date made
1988
product expiration date
1988-03
maker
Schering Corporation
ID Number
1987.0781.02
catalog number
1987.0781.02
accession number
1987.0781
Roferon-A is an injectible, recombinant pharmaceutical used to treat different types of leukemia, malignant melanoma, multiple myeloma, non-Hodgkin's lymphoma, AIDS-related sarcoma, and hepatitis.
Description (Brief)
Roferon-A is an injectible, recombinant pharmaceutical used to treat different types of leukemia, malignant melanoma, multiple myeloma, non-Hodgkin's lymphoma, AIDS-related sarcoma, and hepatitis. It was discontinued in October 2007, as new therapies for the diseases it treated were developed.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human interferon are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferon, which is harvested and used as the active ingredient in Roferon-A.
Object consists of a sealed white cardboard box with red and black print.
Location
Currently not on view
date made
ca 1988
product expiration date
1988-06-01
maker
Hoffmann-La Roche
Roche Laboratories
ID Number
1987.0786.03
accession number
1987.0786
catalog number
1987.0786.03
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur.
Description (Brief)
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human white blood cell interferons are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferons, which are harvested and used as the active ingredient in Intron A.
Object consists of a cardboard box containing a second box, two glass bottles (one of the active pharmaceutical and one of the dilutent), and two product inserts.
Location
Currently not on view
date made
1988
product expiration date
1988-03
maker
Schering Corporation
ID Number
1987.0781.01
accession number
1987.0781
catalog number
1987.0781.01
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur.
Description (Brief)
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human white blood cell interferons are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferons, which are harvested and used as the active ingredient in Intron A.
Object consists of a cardboard box containing a second box, two glass bottles (one of the active pharmaceutical and one of the dilutent), and two product inserts.
Location
Currently not on view
date made
1988
product expiration date
1988-03
maker
Schering Corporation
ID Number
1987.0781.03
accession number
1987.0781
catalog number
1987.0781.03
Currently not on view
Location
Currently not on view
date made
ca 1985 -1990
maker
Hybritech, Inc.
ID Number
2014.0247.12
accession number
2014.0247
catalog number
2014.0247.12
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur.
Description (Brief)
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human white blood cell interferons are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferons, which are harvested and used as the active ingredient in Intron A.
Object consists of cardboard box containing a second box, two glass bottles (one of the active pharmaceutical and one of the dilutent), and two product inserts.
Location
Currently not on view
date made
1988
product expiration date
1988-03
maker
Schering Corporation
ID Number
1987.0781.04
accession number
1987.0781
catalog number
1987.0781.04
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur.
Description (Brief)
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human white blood cell interferons are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferons, which are harvested and used as the active ingredient in Intron A.
Object consists of a cardboard box containing a second box, two glass bottles (one of the active pharmaceutical and one of the dilutent), and two product inserts.
Location
Currently not on view
date made
1988
product expiration date
1988-07
maker
Schering Corporation
ID Number
1987.0781.05
accession number
1987.0781
catalog number
1987.0781.05
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur.
Description (Brief)
Intron A is an injectible recombinant pharmaceutical used to treat hairy cell leukemia.
Recombinant pharmaceuticals are created by inserting genes from one species into a host species, often yeast or bacteria, where they do not naturally occur. The genes code for a desired product, and therefore the genetically modified host organisms can be grown and used as a kind of living factory to produce the product. In this case, genes coding for human white blood cell interferons are inserted into bacteria. Interferon is a substance that is naturally made by the body to fight infections and tumors. Bacteria produce the interferons, which are harvested and used as the active ingredient in Intron A.
Object consists of a cardboard box containing a second box, two glass bottles (one of the active pharmaceutical and one of the dilutent), and two product inserts.
Location
Currently not on view
date made
1988
product expiration date
1988-07
maker
Schering Corporation
ID Number
1987.0781.06
catalog number
1987.0781.06
accession number
1987.0781

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