The Therapy
When a decision has been made in favour of antibody therapy in the context of a disease, a number of preliminary examinations must first be carried out. These should exclude health problems that would speak against the implementation of antibody therapy. The antibodies are administered in the form of injections or infusions, often in combination with the administration of drugs to prevent an allergic reaction.
If the therapy is administered in the form of injections (i.e. syringes), this can also be carried out independently at home by the patient under certain circumstances. Administered several times and, depending on the disease and depending on the antibodies, at intervals of one or several weeks. Depending on the patient’s state of health and the side effect profile of the antibody, checks are carried out at the individual appointments to monitor the body’s reaction to the therapy and the occurrence of side effects.
The duration of antibody therapy varies depending on the disease to be treated, the antibody used and the course of the disease under therapy. Sometimes it is only a few months, whereas the treatment of breast cancer with trastuzumab, for example, is designed to last one to two years. The duration of the individual appointments is also highly variable, depending on the antibody used and the type of application: While injections (syringes) are done very quickly, infusions can take several hours.
In the latter case, therefore, you should take some occupation to pass the time. Depending on which disease is treated with antibody therapy and which antibodies are used, different side effects can occur. Especially in the initial phase of treatment, for example, there may be symptoms similar to those of a flu-like infection, such as fever, fatigue or aching limbs.
Fields of application
The antibody trastuzumab (trade name Herceptin®) has been approved for several years for the treatment of early-stage breast cancer. Trastuzumab binds to HER2/neu, a molecule on the surface of breast gland cells. This molecule is only present in small numbers in the healthy female breast and regulates cell growth.
“Degenerate” mammary gland cells, i.e. breast cancer cells, have a much higher number of HER2/neu molecules on their surface in about 20-25% of cases; this is known as overexpression. This leads to uncontrolled growth of the tumour. By binding to the HER2/neu molecule, trastuzumab inhibits its growth-promoting effect and also labels the breast cancer cell for the body’s own immune system.
This first blocks tumor growth and then causes the body to defend itself against the tumor. To find out whether trastuzumab antibody therapy is at all suitable for a breast cancer patient, the HER2/neu status of the tumour must first be determined. This means nothing other than examining whether the tumour has an above-average number of HER2/neu molecules on its surface, because only then does therapy with trastuzumab make sense.
The simplest procedure for this consists of removing a tiny piece of tissue from the tumour (biopsy) and then staining it to make the HER2/neu molecules visible. The more molecules present, the stronger the colour reaction, so that the result can be expressed in the form of a scale. 0 and 1 indicate a non-exceeded presence of HER2/neu, while 3 indicates that trastuzumab therapy is possible.
A value of 2 requires a genetic examination (FISH) to be connected to clarify the appropriateness of trastuzumab therapy. This does not mean, however, that trastuzumab therapy is fully recommended for all patients with HER2/neu overexpression; other factors such as the extent of the disease or existing secondary diseases play an important role (for example, unrestricted pumping function of the heart is a prerequisite for the use of trastuzumab), so that a decision on trastuzumab therapy should always be based on an individual assessment by a specialist. Trastuzumab is administered as an infusion.
The first infusion takes about 90 minutes and all others about 30 minutes. The infusions are given either weekly or every 3 weeks. As a rule, antibody therapy is not seen as an alternative to chemotherapy, but rather as a supplement: In this case, surgical removal of the tumour is followed by chemotherapy and then, at intervals of about 3 months, antibody therapy.
The antibody Bevacizumab (Avastin®) exists for the treatment of advanced breast cancer. The antibody inhibits the effect of VEGF, a growth factor for the formation of new blood vessels in tumours, and thus practically “starves” the tumour. It is used in advanced breast cancer patients to inhibit the growth of metastases in combination with the chemotherapeutic agent paclitaxel.
Cetuximab, pertuzumab and denosumab are also currently in the final phase of clinical testing and could be included in the treatment regimens for breast cancer in the coming years. The antibodies atezolizumab and nivolumab represent a new and promising option for the treatment of lung cancer. The antibodies bind to a specific surface molecule of lung cancer cells and thereby mark these cells for degradation by the body’s own defence cells.
It should be noted that antibody therapy with acetolizumab or nivolumab is not suitable for all cases of lung cancer: So far, the indication (area of application) has been limited to advanced and/or metastatic non-small cell lung cancer (NSCLC), i.e. to late stages of a certain type of lung cancer. Both antibodies are administered by infusion. The term lymphoma covers a huge spectrum of different malignant diseases of the lymphatic system and just as many different therapeutic strategies.
Currently, there are three antibodies that are approved for the treatment of some types of lymphoma in the category of non-Hodgkin’s lymphomas: Rituximab, Obinutuzumab and Ofatumumab. All three antibodies exert their effect by docking to the CD20 molecule on the surface of lymphoma cells, marking the cells for degradation by defence cells. Rituximab is used for the treatment of follicular lymphomas and diffuse large B-cell lymphomas.
It is used either alone or in combination with chemotherapy in the R-CHOP regimen (where R stands for rituximab and CHOP for the first letters of the chemotherapeutic agents used). Obinutuzumab and Ofatumumab are used in chronic lymphatic leukemia, which is also a subtype of non-Hodgkin’s lymphoma, and in follicular lymphoma. A prerequisite for antibody therapy with one of the antibodies is not only the assignment of the lymphoma to one of the two classes mentioned, but also the biotechnological detection of the CD20 molecule on the cells of the tumor.
For this purpose, a tissue sample (biopsy) must be taken. In advanced colorectal cancer, an intravenous (i.e. administered by infusion) antibody therapy with cetuximab or panitumumab may be considered. Both substances block the binding site of the growth factor EGF on the surface of the cancer cells and thus stop tumour growth.
The antibodies can either be given directly as a supplement to the standard therapy according to the FOLFOX or FOLFIRI regimen or alone following the standard therapy if the latter has not shown sufficient success. Prerequisites for the administration of cetuximab or panitumumab are firstly the presence of the EGF binding site on the cancer cells (this is the case in > 90% of colon cancer cases) and secondly the absence of a K-Ras mutation. This mutation renders cetuximab and panitumumab practically ineffective, so that such a mutation must be ruled out before starting therapy with these antibodies.
Antibody therapy can usually be carried out on an outpatient basis, with weekly (cetuximab) or fortnightly (panitumumab) infusions, each of which takes about half an hour to two hours. The therapy is continued as long as it is effective and does not cause too many side effects. An alternative to the treatment of advanced colorectal cancer with metastases is the antibody Bevacizumab.
This antibody is directed against the vascular growth factor VEGF, thereby inhibiting the vascular growth of the tumour and “starving” it out. Bevacizumab is administered as an infusion and usually in combination with chemotherapy in the form of 5-fluoruracil. In the case of advanced stomach cancer, antibody therapy may be considered under certain circumstances.
This option is usually chosen when the cancer is so advanced that surgery is no longer possible, or when chemotherapy and radiation have not shown sufficient effect. The antibodies trastuzumab and ramucirumab are approved for this application. Trastuzumab stops the growth of cancer cells and is used in combination with chemotherapy in metastatic stomach cancer.
It is administered as an infusion every three weeks and the therapy can be continued as long as the drug is effective. However, this antibody is only effective in the proportion of gastric cancer patients whose tumour cells have the antibody’s specific target molecule on their surface. This must therefore be clarified by means of a tissue sample (biopsy) before trastuzumab therapy is started.
Another aspect that might make the use of trastuzumab impossible is the presence of heart damage. This too will therefore be checked before starting therapy. Ramucirumab is effective against the vessel growth factor VEGF.
This inhibits the formation of blood vessels in the tumour and the tumour “starves”. The antibody can be administered in combination with a chemotherapeutic agent. It is administered in the form of regular infusions at two-week intervals and is continued for as long as it is effective.
In patients with Crohn’s disease, antibody therapy may be considered if the standard therapy with cortisone preparations, amino salicylates (5-ASA) and immunosuppressive drugs (e.g. methotrexate or azathioprine) has not shown satisfactory results or has caused too severe side effects. Infliximab or Adalimumab can then be used. Both drugs belong to the group of TNF-α antibodies.
They are therefore effective against TNF-α, one of the decisive inflammatory substances involved in the development of chronic intestinal inflammation in Crohn’s disease. The antibodies are administered as an injection directly into the blood or under the skin. Since 2014, another antibody for the therapy of Crohn’s disease, vedolizumab, has been available.
Its field of application is limited to moderate to severe cases in adults when standard therapies including TNF-α antibody therapy were not sufficiently effective or had too many side effects. The antibody prevents the transfer of inflammatory cells into the intestinal tissue. In contrast to the TNF-α antibodies, vedolizumab is administered as an infusion lasting about 30 minutes.
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In recent years, several antibodies have been developed that can be used in psoriasis. They are usually used as an alternative when standard measures such as the application of local therapeutic agents, UV therapy or the taking of immunosuppressive drugs have not shown sufficient effect or have caused too strong side effects. The class of TNF-α antibodies is directed against the inflammation factor TNF-α, which plays an important role in the development of psoriasis.
Infliximab, Etanercept, Adalimumab, Golimumab and Certolizumab belong to this group. In addition, there are the antibodies ustekinumab, secukinumab, tildrakizumab and ixekizumab, which are directed against certain inflammatory messengers and thus prevent the activation of inflammatory cells in psoriasis. Speak to your treating physician about the possibility of antibody therapy.
Together with him you can decide whether an antibody therapy is suitable for you and which antibody is best suited to you, especially with regard to the side effect profile. Regardless of the antibody selected, antibody therapy is often combined with the administration of the immunosuppressive agent methotrexate. Depending on the antibody, the administration is carried out as an infusion or injection.
The research on possible applications of antibody therapy for the treatment of neurodermatitis is still more or less in its infancy. Dupilumab is intended to accelerate the healing of skin damage and has also been approved in Germany for moderate to severe neurodermatitis since 2017. The antibody is administered regularly at 14-day intervals in the form of an injection (syringe) under the skin.
Another antibody, nemolizumab, on the other hand, is designed to specifically combat the itching that often accompanies the disease. The antibody is currently being tested on selected patient groups, but has not yet been approved for general use. In rheumatism and rheumatoid arthritis, antibody therapy may be considered if the basic therapeutic agents (painkillers, cortisone preparations and DMARDs such as chloroquine, leflunomide, sulfasalazine or methotrexate) do not have a satisfactory effect or have too strong side effects.
TNF-α antibodies, for example, can be used to combat the inflammatory process by intercepting the inflammation factor TNF-. This class includes the active substances adalimumab, etanercept, infliximab, golimumab and certolizumab. In addition, the antibodies Abatacept, Rituximab and Tocilizumab, which also alleviate the inflammatory process in various ways, are approved.
Common to all antibodies is that they are often administered in combination with methotrexate in the treatment of rheumatism. The antibodies usually take effect within a few days, which is significantly faster than the above-mentioned basic therapeutics. In the first weeks of administration, however, side effects may occur, which usually manifest themselves as a flu-like infection.
Currently, two antibodies are available which can be used in osteoporosis. Denosumab is approved for two situations: For osteoporosis in post-menopausal women and in men after androgen deprivation therapy as a result of prostate cancer. The antibody inhibits the activity of cells that break down bone substance, the so-called osteoclasts.
Denosumab is administered under the skin every six months in the form of an injection (syringe). The antibody Romosozumab has not yet been approved in Germany, but is currently undergoing intensive research. It is expected to have a particularly strong effect in women who have reduced bone density after menopause as a result of hormonal changes.
The antibody promotes the activity of those cells that are responsible for the formation of bone substance. These cells are known as osteoblasts and to a certain extent represent the antagonist of the osteoclasts described above.
