What are monoclonal antibodies ? definition:
A monoclonal antibody is a type of protein made in the laboratory that can bind to substances in the body, including cancer cells. There are many types of monoclonal antibodies. A monoclonal antibody is made so that it binds to a single substance. Monoclonal antibodies are used to treat certain types of cancer. They can be used alone or to carry drugs, toxins or radioactive substances directly to cancer cells.
There are five classes of immunoglobulins (isotypes) of antibody molecules in serum: IgG, IgM, IgA, IgE and IgD. They are distinguished by the type of heavy chain they contain. IgG molecules have heavy chains called γ chains; IgM has μ chains; IgAs has α chains; IgE has e chains; and IgD has δ chains. The variation in heavy chain polypeptides allows each class of immunoglobulins to function in a different type of immune response or during a different stage of the body’s defense. The amino acid sequences that confer these functional differences are located primarily in the Fc domain.
Antibody classes also differ in their valence, the number of arms available to bind to the antigen. This is due to the ability of some immunoglobulins to form multimers by binding their Fc domains via a J chain. For example, IgM is a pentamer of five identical « Y »-shaped monomers. Therefore, the complete IgM protein contains 10 heavy chains, 10 light chains and 10 antigen-binding arms (giving IgM a valence of 10).
IgA (immunoglobulin A)
IgA or « immunoglobulin A » is a group that accounts for about 15% of the antibodies in the blood. They are also found in saliva, tears, respiratory and gastric secretions, and breast milk. IgA provides protection against infections of the respiratory mucous membranes (sinuses and lungs) and gastrointestinal (stomach and intestine) infections. Transmitted by the mother through breastfeeding, IgA protects the digestive tract of the newborn. IgA levels are interpreted by taking into account the levels of IgG and IgM, the other two main classes of antibodies.
IgD (Immunoglobulin D)
The () is a monomeric antibody isotype that is expressed in the plasma membranes of immature B lymphocytes. L’ is also produced in a secreted form that is found in small amounts in blood serum. The secreted form consists of two delta heavy chains and two light chains.
IgE (immunoglobulin E)
Immunoglobulin E (IgE) is a class of antibodies found only in mammals. As proteins of the immune system, they can sometimes be dangerous when they cause severe allergies.
IgG (immunoglobulin G)
IgG (immunoglobulin G) accounts for 70-80% of the antibodies present in the blood. They are produced during the initial exposure to the antigen (often a bacterium or virus) and then increase in a few weeks before stabilizing. The body keeps a « catalogue » of IgG antibodies that can be produced quickly if exposed to the same antigen. IgG is therefore the basis for long-term immunity and vaccination. IgG levels are interpreted by taking into account the levels of IgA and IgM, the other two main classes of antibodies.
IgM (immunoglobulin M)
IgM (immunoglobulin M) is the body’s first response to a « foreign » antigen. They are produced during initial exposure to the antigen (bacteria, viruses, etc.), increase within a few weeks and are replaced by IgG. IgM levels are interpreted by taking into account the levels of IgA and IgG, the other two main classes of antibodies.
What is the use of monoclonal antibodies?
Monoclonal antibodies or monoclonal antibody are identical because they are produced by a clone of specialized cells of the immune system (plamocytes). Monoclonal antibodies are widely used in biology and medicine, both as diagnostic tools and for therapeutic purposes.
The production of these antibodies in-vitro is very difficult because of the short lifespan of plasma cells.
In-vivo production of these antibodies can be obtained by injecting a given antigen into the animal and then extracting it from the blood. This method is very expensive and very few antibodies are obtained.
The development of the hybridoma technique by Caesar Milstein and Georges köhler in 1975 made it possible to obtain a large quantity of antibodies at low cost and thus make it possible to use them in many applications.
This technique consists of injecting the antigen of interest into a mouse and then, after a few weeks, removing the cells from the spleen. Among these cells are plasma cells secreting antibodies specifically directed against the chosen antigen. These plasma cells are fused with tumour cells called myeloma cells (immortal cells) by the addition of polyethylene glycol (PEG), which induces membrane fusion, resulting in hybridomas which have the ability to multiply faster than normal antibody-producing cells of the body and to develop specific antibodies indefinitely. The cells are then distributed in multi-well plates in such a way that there is only one cell per well. A selective culture medium (HAT culture medium) is used to remove plasma cells and unfused myeloma cells. Unfused plasma cells die rapidly and the myeloma cells used that have a non-functional gene for an enzyme involved in nucleotide synthesis-hypoxanthine-guanine-phosphoribosyl-transferase (HGRPT) are unable to survive in HAT (hypoxanthine aminopterin thymidine) medium.
Only hybrid cells multiply. After about 10 days, each well is tested for the presence of antibodies to the antigen used to immunize the mouse. The producing cells are transplanted. A few clones of the producing cells are then isolated and can be preserved in liquid nitrogen.
– Ovulation test: Monoclonal anti-luteinizing hormone antibodies that reveal an increase in the level of LH hormone (an early warning sign of ovulation).
– Pregnancy test: The principle is based on the detection of the hormone hGC (Human Chorionic Gonadotropin) in the urine by means of a specific colour reaction using anti-hGC monoclonal antibodies.
– Manufacture of monoclonal antibodies against antigens carried by tumour cells in order to destroy them. The interest of using monoclonal antibodies for anti-cancer treatment lies in their specificity to destroy target cells. Antibodies can either be used alone (naked antibodies) which, by attaching to the cell, cause its death, or combined with another molecule such as a toxin or radioactive product. In this case, the antibody is used to bring to the tumour cell the element that will destroy it.
– ELISA test: use of monoclonal antibodies as tracer antibodies in the ELISA (Enzyme Linked Immunosorbent Assay). This type of test is used, for example, to detect the presence of anti-HIV antibodies in serum.
Since most monoclonal antibodies are produced in rodent cells, an immune reaction can be observed when they are injected into a patient. This immunity gradually inactivates the beneficial action of the monoclonal antibody. To remedy this problem, « chimeric » or « humanized » antibodies are produced.
Chimeric » antibodies are obtained by grafting constant parts of human immunoglobulin onto the variable parts of a mouse antibody.
The « humanised » antibodies are produced by microbial fermentation or by transgenic mice containing only a part of the human genes that give rise to the antibodies. They are potentially better tolerated in the human body.
Monoclonal antibodies are molecules naturally produced by the immune system to trigger a targeted attack on a hazard already encountered. It soon became apparent that, when properly selected, these homing heads could not only identify tumour cells, but also block their growth. This is the case with trastuzumab, an antibody that binds to the HER-2 protein found on the surface of tumour cells in about 15% of women with breast cancer. Acting as a switch, trastuzumab blocks the action of its membrane receptor, inhibiting tumour growth. It has greatly improved the vital prognosis of these patients since the early 2000s.
Identical strategies have been developed for the treatment of lymphomas, using retuximab, for ENT and colon tumours with antibodies targeting the EGF (Epidermal Growth Factor) receptor. Also the vascularization necessary for development can be targeted with an antibody targeting the VEGF, vascular endothelial grothw factor (bevacizumab, AVASTIN®) to block the growth of many tumors (lung, breast, colon etc…).
Another idea that is beginning to prove its worth is to use antibodies to carry a therapeutic molecule – a chemotherapy or radioactive product.
« The presentation of the results of the EMILIA trial evaluating the efficacy of the T-DM1 molecule, coupling trastuzumab to chemotherapy in patients with HER-2 overexpressing breast cancer, was one of the major elements of the 2012 cancer research agenda, » says Christophe Le Tourneau. Like Herceptin®, T-DM1 binds to HER2 and blocks tumor cell proliferation, but in addition it delivers a chemotherapeutic agent directly into these cancer cells.
Targeting the interleukin pathway
Interleukin 2 (IL-2) is already used to treat some cancers. Eliane Piaggio’s translational immunotherapy team plans to use antibodies to modify the IL-2 induced signaling cascade with funding from the French National Research Agency. Once the first humanized anti-IL-2 antibodies have been developed, her team plans to study the activation of the immune system using an IL-2/anti-IL-2 complex.
There are many approaches based on antibodies, which could lead to new solutions for the treatment of cancers. These are all avenues that need to be explored, developed and personalized through collaboration between physicians, biologists and chemists. Progress will most certainly come from the combination of several therapeutic strategies.
How are monoclonal antibodies made?
Unlike chemically synthesized drugs, monoclonal antibodies (mAbs) are very large molecules, with inherent complexity due to their size, structure and heterogeneity. Complex, their manufacturing process therefore makes use of genetic engineering and cell culture. A living model Mabs are molecules that require the cellular machinery to be fully active: if the genetic code gives the sequence of amino acids leading to the antibody protein chain, many post-translational modifications take place to lead to an effective antibody.
This is why biotechnology uses living, non-synthetic models to produce MAbs. Production in industrial quantities To produce mAbs in large quantities, a large stock of cells capable of producing the chosen antibody is therefore required. For this, biotechnology uses an animal model – the mouse – which it modifies by genetic engineering.
They can also use viruses, phages, which, after genetic manipulation, are capable of expressing the required antibodies on their surface (phage¬display technique).
The stages of production
Step 1: This is achieved by creating transgenic mice or rabbits in which human gene sequences have been inserted instead of murine sequences to produce a specifically human antibody.
From this, a primary cell line expressing the therapeutic monoclonal antibody target is obtained. Since this lineage does not have the capacity to reproduce, it is fused with lymphoid myeloma cells, which have the particularity of multiplying rapidly and indefinitely: we then obtain a cell called a « hybridoma », which knows how to produce the chosen monoclonal antibody and can reproduce indefinitely.
Steps 2 & 3 From this step on, the culture can then begin in a sterile, liquid medium with a mixture of specific growth factors for the cells to multiply. The culture is carried out first in flasks of less than one litre, then in increasingly larger containers to produce very large bio-incubators. At this point in the production process, a specific nutrient medium can be added for optimized production of the selected antibody.
Step 4 Once this mass production has been completed, the antibody chosen to be produced should be specifically selected and extracted from the culture medium (cells, waste, fluids). For this purpose, centrifugation, purification (by chromatography or precipitation) and concentration steps are successively applied to the culture medium, resulting in the purification of the antibody. Several grams of antibody can be obtained from about 100 liters of supernatant .
Step 5 These Mabs are then packaged in a stable form (liquid, powder) in vials ready for distribution.
What are the monoclonal antibody treatments?
Rheumatoid arthritis is an autoimmune inflammatory disease characterized by chronic inflammation of the synovium, which leads to progressive bone erosion, resulting in disability and impaired quality of life. It is a disease that progresses in relapses. Treatment is aimed at controlling pain and inflammation to slow and stop the progression of joint destruction.
MAbs used in this indication:
Adalimumab (Humira®, Truxeda®) Certolizumab Pegol (Cimzia®) Etanercept (Enbrel®)
Anakinra (Kineret®) Infliximab (Remicade®) Rituximab (Mabthera®) Tocilizumab (Roactemra®)
Ankylosing Spondylitis is a painful inflammatory rheumatic disease that mainly affects the spine and sacroiliac joints of the pelvis. It is a condition that begins around the age of 26, and affects men and women equally. The first signs of the disease are characterized by spinal pain that occurs at night, a feeling of stiffness upon waking, or enthesitis (inflammation of the entheses). Extra-articular locations may occur during a spondylarthritis: skin (psoriasis), eye (uveitis), and intestinal (diarrhea) damage are common. The first-line drug treatment consists of non-steroidal anti-inflammatory drugs (NSAIDs). Background treatments based on methotrexate and sulfasalazine as well as anti-TNFs are used when NSAIDs are not sufficiently effective. Non-drug treatment is equally important, with the possibility of receiving corticosteroid infiltrations. Rehabilitation is recommended.
MAbs used in this indication:
Adalimumab (Humira®, Truxeda®) Golimumab (Simponi®) Etanercept (Enbrel®) Infliximab (Remicade®)
Psoriatic arthritis is a chronic inflammatory arthritis associated with psoriasis. In most cases, psoriasis precedes the onset of psoriatic arthritis. In all cases, symptoms include pain, stiffness and swelling of the affected joint. MAbs used in this indication : Adalimumab (Humira®, Truxeda®) Golimumab (Simponi®) Etanercept (Enbrel®) Infliximab (Remicade®)
Adult psoriasis Adult psoriasis is a recurrent chronic inflammatory disease that affects the skin, scalp and joints. Psoriasis is characterized by the appearance of scaly patches. Its etiology is not yet fully elucidated but psoriasis is thought to be the consequence of an overproduction of pro-inflammatory cytokines. The severity of plaque psoriasis is most often classified according to the percentage of body surface area affected:
Mild psoriasis is defined as affecting less than 5% of the surface area of the body. Moderate psoriasis affects 5% to 10% of the population. Severe psoriasis is defined as affecting more than 10% of the surface area of the body. MAbs used in this indication : Adalimumab (Humira®, Truxeda®) Infliximab (Remicade®) Etanercept (Enbrel®) Ustekinumab (Stelara®) Juvenile Idiopathic Arthritis Juvenile idiopathic arthritis is a form of arthritis that affects children under 16 years of age and persists for at least 6 weeks.
Three subtypes exist in this pathology: the pauci articular form where less than 5 joints are affected, the poly articular form which affects 5 or more joints, and the systemic form which corresponds to arthritis, with fever and rashes.
MAbs used in this indication : Adalimumab (Humira®, Truxeda®) Etanercept (Enbrel®) Tocilizumab (Roactemra®)
Systemic Lupus Erythematosus
Systemic lupus erythematosus is an autoimmune disease affecting women in particular (9 times out of 10) between the ages of 20 and 40. This disease is polymorphic and its clinical course is variable from subject to subject, however the presence of antinuclear autoantibodies and anti-DNA antibodies is common. Skin and joint lesions as well as vascular lesions (Raynaud’s phenomenon, purpura, leg ulcers and more rarely alopecia) may also be observed.
This condition can progress to severe visceral forms with renal, cardiological or neurological damage.
MAb used in this indication: Belimumab (Benlysta®)
Multiple sclerosis is a demyelinating inflammatory disease of the central nervous system that is the leading cause of non-traumatic disability. This disease usually progresses in relapses, with recovery of part of the neurological deficit. The average age of onset is 30 years. This pathology affects women twice as much as men. In 85% of patients, multiple sclerosis begins with a reversible and episodic neurological dysfunction, evoking the relapsing-remitting form.
In 75% of these patients, the disease progresses over time to stabilize with irreversible disability, reflecting the progressive form of the pathology. About 5% of patients develop fulminant multiple sclerosis, with rapid onset of severe disability. Finally, 10% of patients diagnosed with multiple sclerosis do not progress. It is then a benign multiple sclerosis.
MAbs used in this indication : Natalizumab (Tysabri®) Alemtuzumab (Lemtrada®)
Crohn’s disease is a chronic inflammatory disease of multifactorial etiology that affects the digestive tract from mouth to anus. It’s a disease that progresses in relapses. Among the main symptoms are abdominal pain, with diarrhea with or without bleeding. Fatigue and weight loss are very common. Treatment is aimed at controlling inflammation, maintaining remission and preventing complications. MAbs used in this indication : Adalimumab (Humira®, Truxeda®) Natalizumab (Tysabri®) Certolizumab Pegol (Cimzia®) Vedolizumab (Entyvio®) Infliximab (Remicade®)
Recto-colitis haemorrhagicus (RCH)
Ulcerative colitis or ulcerative colitis is a chronic inflammatory bowel disease characterized by mucosal ulceration, rectal bleeding, bloody diarrhea and abdominal pain. Unlike Crohn’s disease, UC is limited to areas of the colon and rectum. Treatment aims to reduce and maintain symptom remission, decrease inflammation and prevent complications.
MAbs used in this indication : Infliximab (Remicade®) Vedolizumab (Entyvio®)
Cryopyrin-Associated Periodic Syndromes or CAPS
The term Cryopyrin-Associated Periodic Syndrome (CAPS) is used to describe three diseases: – The cold family auto-inflammatory syndrome – Mückle-Wells syndrome – CINCA syndrome: a multisystemic inflammatory disease with neonatal onset
These are inflammatory diseases linked to mutations in the gene coding for cryopyrin (ICS1 or NLRP3) which activates the inflammasone responsible for the production of IL-1 and IL-18. According to HAS, these pathologies are characterized by the association, in several members of the same family, of cutaneous, articular, neurosensory and neurological signs in a biological context of major inflammation.
MAbs used in this indication: Canakinumab (Ilaris®)
Anti-cancer treatments Colorectal cancer
Colorectal cancer is a tumour affecting the colon and rectum, the incidence of which increases with age. It is the 3rd most common cancer in France with more than 30,000 cases diagnosed each year. It often develops asymptomatically but may be discovered as a result of bloody stools, constipation or worsening diarrhea. Five stages of 0 and IV are used to classify the different stages of colorectal cancer.
Smoking, a personal or family history of cancer, the presence of inflammatory bowel disease and lifestyle habits such as a sedentary lifestyle or a diet high in fat and low in vegetables are major risk factors. Screening is done by a test Hemoccult from the stool. In subjects at risk (history of cancer), colonoscopy is the reference examination for the diagnosis of this cancer. For the early stages of the disease (stage 0 and I) surgery is the reference treatment.
For stages II and III, in addition to surgery, radiotherapy and chemotherapy may be used to reduce the risk of recurrence. For the most severe stage (IV), chemotherapy is often combined with targeted therapy such as monoclonal antibodies.
MAbs used in this indication : Panitumumab (Vectibix®) Bevacizumab (Avastin®) Aflibercept (Zaltrap®)
Lung cancer or bronchial tumour is the most deadly cancer with nearly 37,000 cases diagnosed per year in France. The majority of these cancers are non-small-cell bronchial cancers (80%), the others are small-cell cancers (20%). These are more aggressive and have the potential for significant metastatic disease. Symptoms (purulent sputum, lung infections, coughing fits, dysphonia may suggest lung cancer). There are four stages of classification for non-small-cell lung cancer: I to IV. There are two stages for small cell cancers.
Smoking is the main risk factor for lung cancer. However, other factors such as occupational exposure to metals or gases (nickel, arsenic, tar), air pollution, or genetic factors are not negligible. Bronchial tumours are mainly diagnosed during a chest X-ray, sputum cytology or a chest CT scan. For so-called early non-small cell lung cancers (stage I and II), surgery is the most common treatment.
For locally advanced stages (stage III), chemotherapy is usually combined with surgery. For so-called metastatic Stage IV, chemotherapy is combined with targeted therapy. Localized or metastatic small cell bronchial cancers are treated with chemotherapy.
MAb used in this indication: Bevacizumab (Avastin®)
Breast cancer is a breast tumour that currently affects 1 in 8 women and is the most common cancer in women. It develops in 2/3 of cases in women over 50 years of age. Of the women affected, 25% will develop metastatic breast cancer with a poor prognosis. Any change in the shape of the nipple or the development of a lump in the breast or armpits should be reported to a doctor.
There are three major breast cancer categories: more or less HER2+ positive hormonal luminal cancers, HER2+ cancers and triple negative cancers (hormonal and HER2 negative). Age, the presence of a personal or family history of cancer, poor lifestyle habits (sedentary lifestyle, smoking, alcohol consumption) are the known risk factors for breast cancer. Regular check-ups (palpation and mammography) are the main tests used to detect breast cancer.
Mammography is often combined with an ultrasound. The earlier the cancer is detected, the more likely it is to be cured. Luminal cancers that overexpress hormone receptors are treated with hormone therapy (anti-oestrogen, anti-aromatase, LH-RH analogues). Triple negative cancers representing 15% of breast cancers are treated with chemotherapy but are considered aggressive because they are resistant to current treatments. For HER2+ cancers, targeted anti-HER2 therapies are approved in Europe. The use of anti-VEGF treatment limits the phenomenon of angiogenesis, which slows down the development of the tumour.
MAbs used in this indication : Bevacizumab (Avastin®); Trastuzumab (Herceptin®); Trastuzumab emtansin (Kadcyla®); Pertuzumab (Perjeta®)
Kidney cancer accounts for 3% of all cancers. It’s a tumor that grows from the cells of the renal parenchyma. Known risk factors are smoking, overweight, obesity, age (for those over 65), and gender (men are twice as affected as women), high blood pressure, and hereditary predisposition. Given the rarity of this cancer, there is no screening offered to the general population.
In addition, it is often discovered by chance during an ultrasound, MRI or CT scan. Other symptoms may evoke this diagnosis, such as the appearance of hematuria, fatigue, weight loss, night fevers. The majority (75% of cases) of kidney cancers diagnosed are localized, the remaining 25% are metastatic. When the tumour is local, the nephrectomy may be total or partial. When kidney cancer has metastasized, surgery is usually combined with therapies targeting VEGF growth factor or tyrosine kinases. Bevacizumab is used in combination with immunotherapies such as interferon alpha 2a.
MAb used in this indication: Bevacizumab (Avastin®)
Malignant ascites is characterized by the presence of fluid containing cancer cells in the peritoneum. Malignant ascites are mainly due to a blockage by the cancer cells of the resorption of the peritoneal fluid. In this case, this fluid is mainly composed of proteins and neoplastic cells. Symptoms of ascites may include an increase in abdominal volume, weight gain, nausea or vomiting, or loss of appetite. In order to diagnose this condition, an abdominal X-ray or CT scan may be performed.
The standard treatment consists of intraperitoneal chemotherapy depending on the origin of the tumour (gastric, colic, rectal, ovarian). Catumaxomab is used when tumour cells in the peritoneal fluid overexpress EpCAM.
MAb used in this indication: Catumaxomab (Removab®)
Melanoma is a skin cancer whose incidence has been increasing for decades. It develops from melanocytes, skin cells found in the basal layer of the epidermis and involved in the synthesis of melanin. It is noticeable by the presence of a mole with blurred, irregular contours or non-uniform colours. The different stages of this cancer are classified into 4 categories: from stage I to stage IV. Excessive exposure to X-rays is one of the most important risk factors for the development of the disease. The Caucasian population has a 20 times higher risk of developing melanoma than a person with black skin.
For non-metastatic and localized tumours (stage I and II), surgery, also called extended resection, is the main treatment. Adjuvant immunotherapy with interferon alpha may be offered to reduce the risk of recurrence. For stage III where lymph node involvement is visible, the same treatments can be used. However, chemotherapy is sometimes necessary when the melanoma is not operable. In 20% of cases (stage IV), patients with melanoma develop distant metastases. The appropriate treatment depends on the number and type of metastases. Biologics such as ipilimumab and vemurafenib have been approved in Europe in this context.
MAbs used in this indication: Ipilimumab (Yervoy®)
Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a blood disease characterized by the progressive accumulation of lymphocytes in peripheral blood, bone marrow and lymphoid tissues. CLL is an indolent disease that does not progress rapidly. It accounts for less than 1% of all cancers. Patients are usually diagnosed around the age of 70. It is usually characterized by fatigue.
MAbs used in this indication: Ofatumumab (Arzerra®) Rituximab (Mabthera®)
Non-Hodgkin’s lymphoma is an umbrella term for indolent and clinically expressed lymphomas. Lymphoma is a disease characterized by excessive production of malignant B or T lymphoid cells. The etiology of the disease is not known. The goal of treatment is to improve the prognosis of aggressive lymphomas. Symptoms, which are not characteristic, include fever, night sweats, weight loss, accompanied by lymphadenopathy, hepato-splenomegaly.
MAb used in this indication: Rituximab (Mabthera®)
Grafting is a transplantation without vascular anastomosis of part of a tissue into an individual. If the donor and recipient are two genetically distinct individuals, the term allogeneic transplant is used. Acute graft rejection is the result of an immune system reaction against the graft. This rejection may occur one to several months after transplantation.
MAbs used in this indication: Basiliximab (Simulect®) Belatacept (Nulojix®)
Paroxysmal nocturnal hemoglobinuria
Paroxysmal nocturnal hemoglobinuria is a rare genetic disorder due to an abnormality in the gene coding for phosphatidyl inositol glycanne class A necessary for the anchoring of complement protective proteins (CD55, CD59). Patient cells are therefore more sensitive to complement, especially red blood cells. This pathology evolves by relapses and is characterized by hemolytic anemia, medullary aplasia and generally thrombosis. Haemoglubinuria most of the time causes jaundice which can in some cases end in renal failure. The nocturnal flare-ups are explained by complement dependent hemolysis, which is more pronounced during the night.
MAbs used in this indication: Eculizumab (Soliris®)
Castleman’s disease is a lymphoproliferative disease characterized by hyperplasia of the lymph nodes. Two forms exist, one is called unicentric because it affects only one lymph node, the other is called multicentric, less common but more aggressive. In this disease, there is an overproduction of interleukin 6 (IL-6) in the hyperplastic lymph nodes which is responsible for systemic symptoms (fever, nausea, fatigue, thrombocytopenia, hypoalbuminemia, hypergammaglobulinemia…). When Castleman’s disease progresses it can lead to pancytopenia, multi-organ failure and even lymphoma.
MAb used in this indication: Siltuximab (Sylvant®)
The World Health Organization estimates that 300 million people worldwide currently suffer from asthma. In addition, asthma is the most common chronic disease in children, leading to approximately 250,000 deaths per year. Asthma is a chronic obstructive respiratory disease that involves inflammation of the airways. Allergic asthma is associated with bronchial hyperreactivity linked to the binding of the allergen to mast cells or basophils sensitised by allergen-specific IgE antibodies. Clinically it is characterised by recurrent episodes of wheezing, shortness of breath, chest tightness and cough.
MAbs used in this indication: Omalizumab (Xolair®)
Age-related macular degeneration (AMD)
Age-related macular degeneration (AMD) is a condition that affects the cells of the macula, which is the central area of the retina, and allows people to read, write, and visualize details and colours. AMD is the leading cause of visual impairment and blindness in patients over the age of 50. There are three types of AMD :
– The dry or atrophic form, affecting 1/3 of patients, marked by a progressive alteration of the cells of the macula.
– The wet form, known as neo-vascular or exudative, which affects 2/3 of patients, linked to a multiplication of abnormal vessels under the retina and a thickening of the macula.
– Age-related maculopathies, often asymptomatic, characterized by the presence of precursors.
MAbs used in this indication : Bevacizumab (Avastin®) Ranibizumab (Lucentis®) Aflibercept (Eylea®)
Adult bone remodeling is a delicate balance between bone formation by osteoblasts and resorption by osteoclasts. Multiple factors, including hormones, growth factors and cytokines influence and regulate this homeostasis. Osteoporosis is a disease characterized by decreased bone mass, deterioration of skeletal microarchitecture and altered bone strength resulting from increased bone resorption relative to bone formation.
mAb used in this indication: Denosumab (Prolia®)
Lung infection RSV infection
Acute bronchiolitis is a viral infection affecting infants under 2 years of age. They are mainly caused by the respiratory syncytial virus (RSV). This virus is transmitted directly by contaminated respiratory secretions, but also indirectly by the hands of family members or nursing staff. This pathology is benign except for infants with risk factors (prematurity, bronchopulmonary dysplasia, heart disease).
What are examples of therapeutic monoclonal antibodies?
Therapeutic antibodies represent a wide and varied therapeutic arsenal. It is obviously impossible to review the 53 therapeutic antibodies and the 7 proteins fused to an Fc (cf. fusion proteins) which are currently marketed in France and allow the treatment of 51 diseases in 14 therapeutic areas .
Therapeutic indications of the antibodies marketed in France, Diseases have seen their prognosis totally transformed by the advent of anti-therapeutic agents, with improved quality of life for patients with chronic, highly disabling diseases. Antibodies neutralizing the TNF cytokine responsible for inflammation, primarily inflixi-mab and adalimumab, have enabled patients with rheumatoid arthritis or Crohn’s disease to resume normal life.
These drugs are also effective in ankylosing spondylitis and psoriasis. Natalizumab, an anti-lymphocyte adhesion molecule antibody that blocks the migration of lymphocytes to the brain, is one of the best treatments for multiple sclerosis. Elderly people with age-related macular degeneration who are at risk of blindness can now maintain vision thanks to neutralizing antibodies to the vascular endothelial growth factor (VEGF), such as ranibizumab, bevacizumab and aflibercept.
In oncology, progress has also been made. Rituximab has been shown to change the prognosis of lymphomas and trastuzumab is very useful in some forms of breast cancer. By neutralizing VEGF and blocking the proliferation of vessels and blood flow to tumors, bevacizumab is also a useful adjunct to control many cancers. Several antibodies are now being developed that target and block inhibitory T cell receptors, allowing them to « wake up » T cells and allow them to attack cancer cells. This new form of immunotherapy is now providing a great deal of hope for many cancers.
Where to buy monoclonal anticoagulants and at what price?
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