Biological agents & immunotherapy

Home Treatments Lifestyle Symptoms Cancers

 

One of the 1st observations of an immunotherapy reaction was seen at the turn of the 20th century, when a patient's breast cancer shrunk following a severe skin infection. Her bodies defenses where so greatly stimulated to fight the infection they also attacked the tumour. Since then there has been  major strives to enhance this reaction by identifying specific tumour targets (often the tyrosine kinase receptor) and develop antibodies against them called monoclonal antibodies (Mab). Other biological agents attack the specifically attack tyrosine kinase receptors via proteins which are not Mab's these are generally known as tyrosine kinase inhibitors.

 

 

Monoclonal antibodies Trade Name Used to Treat:
Rituximab MabThera

Non-Hodgkin’s lymphoma

Against CD20 antigen found in excess on lymphoma cells. extensively used in both low and high grade lymphomas as long as they are shown to over express CD20 proteins.
Trastuzumab Herceptin

Breast cancer

An intravenous agent, attacking the HER-2 receptor (activity is greatest in tumours also over expressing cMYC, PTEN or TOPO 11.
Cetuximab Erbitux

 

Colorectal cancer

 

An intravenous inhibitor of erbB1(EGFR)
Bevacizumab Avastin Colorectal cancer An intravenous humanised Mab attaches to and inhibits  vascular endothelial growth factor which then prevents new bllod vessels forming in cancers (angiogenesis)
Panitumumab n/a Colorectal cancer A humanised mab against EGFR under investigation
Alemtuzumab Campath Chronic lymphocytic leukemia Active against low grade lymphoma and CLL attacks the CD56 antigen.
Ibritumomab tiuxetan

Zevalin

 

Non-Hodgkin’s lymphoma A Mab which has a radioactive molecule attached to it shown activity in patients with low grade NHL transforming into higher grade tumours
Tositumomab Bexxar Non-Hodgkin’s lymphoma A Mab which has a radioactive molecule attached to it shown activity in low grade NHL.
Tyrosine Kinase inhibitors Trade name Used/ researched 
Gefitinib Irissa Lung & pancreas Inhibits a mutated EGFR (p-Akt).
Erlotinib Tarceva Lung & pancreas Inhibits a mutated EGFR
Imatinib Gleevec GIST & CML An oral agent. Inhibits EGFR with the KIT mutation found in CML and gastrointestinal stromal tumours
Lapatinib Tyverb Breast An oral, dual inhibitor of EGFR (erbB1) & HER2 (ErbB2)
Sunitinib Sutent Renal cell An oral multi-targeted tyrosine kinase inhibitor with activity against vascular epidermal growth factor receptor (VEGFR), platelet derived growth factor receptor, KIT, RET and FLT3 having anti-tumour and anti-angiogenesis activity.
Sorafeneib  

Nexxava

 

Renal cell An oral agent with multiple targets against the tryosine kinase inhibitor.
Other biological agents

 

Trade name    
Temsirolimus n/a   A specific inhibitors of mTOR, a signalling protein that regulates cell growth and angiogenesis.
Bortezomib Velcade   Attacks a structure called the protosome.

 

 

How do Mab's fight cancer cells? They essentially work in a number of ways:-

1) Blocking tumour cell function & growth:  They can bind to receptor proteins on the surface of  tumour cells. These block pathways which reduce the cells ability to grow, spread, invade other organs.
2) Signalling of the immune system: Once bound to cancer cells, the antibody is able to stimulate and recruit the bodies own immune system including natural killer (NK) cells to attack the cells. For this reason treatment with Mab is often called immunotherapy. 
3) Working with chemotherapy:
Antibodies sometimes work with chemotherapy work in a partnership. The chemotherapy kills the DNA and the Mab stops the cells from repairing themselves.
4) Being attached to a other substances. In some cases Mab have been conjugated or joined to another substance which kills the tumour cells. This could be a chemotherapy drug, radioactive particle, or a toxin (a substance that poisons cells).

Preparation for Mab's therapy. As Mab's are specific treatments your doctor needs to find out if your tumour expresses the necessary target before even considering treatment. This is usually achieved by re-analysing a section of your original tumour (from the time of your original surgery or biopsy). Occasionally, your doctor will need a more recent tumour for analysis and recommend a further biopsy. In either case the tumour is usually send to a lab which specialises in specific testing for antigens (targets) called immunohistochemistry. A report will be issued by the pathologist on whether your tumour over expresses the target and to what degree. For example, Herceptin treatment for breast cancer requires the tumour to be HER-2+ve and on a scale of 1-3 it should be 3 to ensure a likely subsequent clinical response. As with other therapies, your Doctors will also check your blood before treatment, to ensure adequate function of your bone marrow, kidneys and liver.

How are Mab administered? Mab cannot be taken orally as they would be destroyed by your stomach. They are therefore infused into a vein usually over a few hours. Occasionally, as with all protein based drugs it is possible to get an allergic reaction. The nurses will therefore be checking how you are feeling and measuring your breathing, pulse and blood pressure blood regularly. If all goes well the infusion can last 1-2 hours, sometimes, in response to mild reaction, it may have to be slowed down over several hours. Rarely if there allergic reaction is prominent it has to be stopped altogether and abandoned. To avoid a mild reaction often paracetamol and an antihistamine are given before the infusion. If you are are able to tolerate the first infusion it will be repeated thereafter, either at the same or a lower dose, on regular intervals. The specific regimen (ie weekly, 3 weekly) will be explain to you by the doctors and nurses and depends on the specific Mab used. Mab are often given in conjunction will chemotherapy the administration schedule and side effect also depend on these drugs.

Are there side effects to Mab therapy? Compared with side effects of standard chemotherapy, the side effects of naked MAbs are usually relatively mild. They can be broadly split into three categories:-

The early effects often related to an "allergic" reaction. If they do occur, it is often while the drug is being infused or . Potential side effects include:

Particularly if associated with a fast pulse and lower blood pressure these symptoms indicate an early allergic reaction. As mentioned above if these symptoms are prominent the infusion has to be slowed down or abandoned altogether. To avoid a mild reaction often paracetamol and an antihistamine are given before the infusion. 

The ongoing effects may occurs over the entire period of time whilst you are receiving the Mab - usually weeks to months. these are usually worse a day or two after the infusion and could include:-

Late side effects may occur occur after receiving Mab for some time - usually months. These include heart & lung damage - they are rare but this is the reason why patients receiving prolonged Mab therapy have special monitoring including Heart test.

How are Mab made? Some patients are interested in the technical aspects of their treatments are made. If you are not please ignore this paragraph. - Antibodies are mass-produced in the lab by fusing a myeloma (a type of bone marrow cancer) cell from a mouse with a mouse B cell that makes a specific antibody. The cell that results from this fusion is called  a hybridoma, from the Latin word hybrid, meaning offspring with parents of different species, and the Greek suffix oma, meaning tumour. The combination of a B cell that can recognize a particular antigen and a myeloma cell that lives indefinitely makes the hybridoma cell a kind of perpetual antibody-producing factory. Because the antibodies are all identical clones produced from a single (mono) hybridoma cell, they are called monoclonal antibodies ( MAbs). 


Further general information Your doctors and specialist nurses are in an ideal position to give you relevant information on your disease and treatment as they know your individual circumstances. Cancerbackup has a help line (0808 800 1234) and a prize winning video available in English, Italian, Urdu, Bengali, Gujarati & Hindi explaining Radiotherapy & Chemotherapy. Cancernet.co.uk has over 500 pages describing cancer, its management, practical tips and tool which patients, their carers and their doctors have found helpful during the cancer journey.


Home | Cancer management | Cancer treatments - Chemotherapy ¦ Radiotherapy ¦ Hormones ¦ Biologicals | Complementary | Lifestyle - Exercise ¦ Diet ¦ Smoking ¦ Sun | Tests for cancer | Books | Videos | Travel | Insurance | Symptoms | Side effects | Clinical trials | Glossary | Support groups & links | About cancer | About us | Disclaimer