Monoclonal Antibody – Alternatives for Treating Non-Hodgkin’s Lymphoma

Non-Hodgkin’s lymphoma or NHL is a serious affection which occurs due to the presence of B cells (B lymophocytes), a type of white blood cells which usually lead to severe complications such as tumors. Even though, treatments with chemotherapy and radiation are considered effective for many people who suffer from NHL, on the other hand for many pantients these procedures can be very toxic.

In addition to this, specialists have developed in the laboratories a new theraphy to treat NHL, a theraphy known as Monoclonal-antibody which has been proved to be safe and effective for certain patients. As we know the body produces antibodies, substances which have the role to fight against bacteria and viruses. Moreover, monoclonal antibodies have been produced in laboratories like many other antibodies and have the role in producing anti-tumor effects. Since most NHL patients have B cells, treatment with monoclonal-antibodies has brought important results in healing lymphoma and much more they have been prescribed with other toxin or radioactive particles that usually kill cells.

Furthermore, monoclonal antibody treatments usually include medications as Rituxan or Bexxar. First of all, treatments with Rituxan are considered very effective for people who suffer from NHL and may be used for other types of lymphomas too. Rituxan is the only monoclonal antibody treatment approved for NHL and most of the time has been studied in patients that have relapsed low grade NHL. Moreover, it can be taken without other medicines and it is usually given intravenously once a week for 4 weeks. In contrast to other procedures, Rituxin doesn’t offer serious side effects such as hair loss, vomiting, and low blood counts.

Secondly, another monoclonal antibody which is being tested in laboratories is Bexxar. This medicine is a murine monoclonal antibody and doesn’t have a naked form due to the presence of a radiocative iodine molecule which is attached to it. Just like Rituxan, this agent is administered intravenous with the first dose having a trace amount of radioactivity and the second dose containing most of the radioactive iodine. On the other hand, Bexxar has some negative aspects, such as fever, chills or shakes and in some cases NHL patients may have temporary drop in blood counts.

Thirdly, another monoclonal antibody which has been studied as NHL treatments is Oncolym. This agent has been studied in a radiolabeled form like Bexxar and has proved to be toxic like other radiolabeled antibodies. In contrast, LL2 is a humanized antibody, using a naked, unlabeled form as well as a radiolabeled form.

To conclude, monoclonal antibodies can be very effective in treating NHL due to their low toxicity and also the advantage of combining them with each other and also by using them in combination with chemotherapy or other procedures. It is important to say that people who suffer from NHL should be aware of their condition and become well-informed in order to follow the suitable treatment.

P53 Antibody – The Multi-Cellular Organism

P53 antibody – P53, also identified as tumor protein 53, is a tumor suppressor protein that is encoded by the TP53 gene in humans.

The gene is highly conserved in vertebrates with sequences found in invertebrates showing only a distant resemblance to mammalian forms of the gene. P53 is crucial in multi-cellular organisms where it plays a crucial role in DNA damage repair and anticancer function. During the DNA synthesis phase of cellular division in the event of DNA damage P53 is activated. P53 arrests the cell cycle in the S-phase of the cycle and activate DNA repair proteins to repair any damages before allowing the cell cycle to continue. Moreover, P53 can also initiate apoptosis, programmed cell death, if DNA damage cannot be repaired, preserving genomic stability.

Additionally, it also becomes active if factors such as stress, (osmotic) shock, and deregulated oncogene appearance occur. P53 also functions in the inhibition of angiogenesis, which is the formation of new blood vessels that is crucial in the growth and metastasis of cancer and tumors.

The mouse monoclonal antibody can be used to visualize the P53 tumor antigen quantities in a broad selection of transformed cells. In addition, the protein is visible in many dynamic proliferating non transformed cells.

However, it is undetectable or present at low levels in resting cells. This protein induces cell cycle arrest or apoptosis in response to sublethal or severe DNA damage, respectively, by differential transcription of target genes and through transcription-independent apoptotic functions. The P53 protein contains 393 amino acids, and the human P53 tumor antigen is located at band 17p13.

P53 mutations or deletions play a crucial role in the development of cancer, as well as cancer diagnostics and research. P53 malfunctions are common in pancreatic cancer, in addition to Li-Fraumeni syndrome. Li-Fraumeni syndrome is caused by the damage in the P53 tumor suppressor gene. If an individual is diagnosed with this syndrome then they are 25 times more likely to develop a malignant tumor by the age of 50. This syndrome is characterized by several different cancers i.e. breast cancer, and acute leukemia. Diagnosis of Li-Fraumeni syndrome includes if the patient has been diagnosed with sarcoma below the age of 45, which is a cancer that arises from transformed cells of mesenchymal origin. Other possible developments can lead from first or second degree family members that have had cancer at a young age.

Recommendations for Li-Fraumeni syndrome includes avoiding radiation therapy, which can diminish the risk of secondary radiation induced malignancies. In addition, other prerequisite proposals that have to be done to prevent Li-Fraumeni syndrome are annual physical examination, for women to start breast cancer monitoring from age 25, and to consult with a physician if any illnesses or symptoms arises.

The P53 antibody host is from a mouse, and can be tested on other species for research use only. The P53 antibody can be tested on a range of applications, such as WB (western blot), IHC-P (immunohistochemistry), and P-Elisa.

Long Term Space Flight and Human Biosystem Antibodies – Deal Breaker or Is There a Solution?

NASA’s Astrobiological division certainly has some bugs to work out, literally with long-term human spaceflight. If we are going to create 100-years spaceship, and boldly travel to places that no human has ever been, then obviously we need to keep those humans alive for the duration of that trip. There are so many challenges involved it seems a bit overwhelming, but maybe it’s not, maybe we just aren’t thinking this through properly. Yes, we have the best minds in the business working on it, but maybe they aren’t thinking outside the box anymore.

Now then, there are those that work in NASA and have been working on these things for decades, and that last statement might almost be a slap in the face to their hard work. I don’t doubt for a second that they have learned all kinds of wonderful things, things which have not only helped the space program, but things which are also saving lives here on earth in the healthcare industry. Any time we do this sort of research, we learn more about the human body, and the human biosystem.

There was an interesting article in SpaceDaily – Your Portal to Space” which was filed under the category of; Space Medicine, and article was titled; “Antibody Production Gets Confused During Long-Term Spaceflight,” by Staff Writers in Bethesda, MD published on May 20, 2011. The article stated;

“Antibodies produced in space are less effective than those produced on terra firma. Reduced effectiveness of antibodies makes astronauts more susceptible to illness, while increasing the danger posed by bacteria and viruses likely to coexist with wayfaring astronauts.”

Obviously, a weakened immune system is a real problem in space, much more than it is here on Earth. What the researchers found was that “the antibodies generated by the group immunized in space was decreased. The spaceflight conditions alter the immune system and its ability to protect against infections and tumors, posing a serious risk for astronauts.”

Okay so, let me throw out some thoughts here if I might specifically, “WHAT IF” – yes, I know big words, but what if the anti-body production in long-term space flight had to do with light, circadian rhythm, and the Earth’s frequency? What if those exact conditions were exactly mimicked during long term space flight, along with some artificial gravity scheme?

Yes, these are the questions I believe we need to address when it comes to long-term space flight. Most are, but when it comes to this particular problem, it seems these are things we should be asking ourselves.

What about the human innate evolutionary bonding to the extremely low frequencies of planet Earth, the planet has a specific resonance too. Surely, the human biosystem along with all its symbiotic relationships will work better and correctly if they are shielded from the radiation and have available the optimized conditions they’ve evolved with. Please consider all this and think on it, let’s get this problem solved so we can von voyage to distant stars.

Antibody Dependent Cell-Mediated Immunity

Hypersensitivity reactions mediated by antibodies fall into different types. These are: anaphylactic reaction, cytotoxic hypersensitivity, Immune complex mediated tissue damage, T-Cell-mediated hypersensitivity, stimulatory hypersensitivity and antibody dependent cell-mediated cytotoxic mechanism (ADCC). What are they?

Type 1: Anaphylactic reaction

Initial introduction of the antigen (e.g, penicillin) leads to the production of cytotoxic antibodies (mainly IgE) in sensitive persons. These are attached to the surface of mast cells.

On subsequent exposure, the antigen reacts with the preformed antibodies, causing mast cell degranulation and release of histamine serotonin, and slow reacting substance (SRSA). This may lead to asthma due to broncho-constriction, or anaphylactic shock due to wide-spread capillary dilatation.

Allergens such as pollens, house dust and fungi react with cell bound IgE of the respiratory tract leading to bronchial asthma or hay fever. Allergens from food may cause urticaria.

Type I hypersensitivity reaction occurs within 30 minutes of exposure to the allergens. Such reaction can be abolished by drugs like adrenaline and disoduim cromoglycate which prevent the release of histamine. Antihistamines compete with the released histamine for effector sites. Repeated introduction of the allergen in small doses results in hyposensitization.

Type II: Cytotoxic hypersensitivity

Certain drugs may complex with membrane proteins of blood cells leading to production of auto-antibodies. These antibodies can lyse the blood cells through the action of complement. Hemolytic anemia caused by alpha methyl dopa, agranulocytosis produced by amidopyrine and thrombocytopenia induced by chlorothiazides are examples of this mechanism.

Type III: Immune complex mediated tissue damage

The continued presence of antigen causes persistent antibody production. Antigen antibody complexes form and circulate in the blood. These heavy molecules are entrapped in the blood vessels, renal glomeruli, lungs, skin and joints.

Complement system is activated through the alternate pathway. The complement degradation products attract polymorphs and macrophages and an inflammatory reaction sets in with resultant damages to the tissues. Platelet aggregation occurs and these microthrombi lead to vascular occlusion and ischemia. If the antibody is in excess, the complexes are rapidly precipitated and tend to be localized at the site of entry of antigen. This leads to Arthus type reaction. If an antigen is injected intradermally into a hyper-immuned animal, erythema and edema occur at the site of the injection.

This reaction reaches a peak in 3-8 hours, and is referred to as intermediate type skin reaction. Farmer’s lung is the classical example of localized type III reaction. On the other hand, if antigen is in excess, soluble complexes are formed which precipitate in all tissues, giving rise to the serum sickness type of reaction. The lumpy granular precipitates seen in renal glomeruli in post-streptococcal glomerulonephritis are due to systemic type III reaction.

Type IV: T-cell-mediated hypersensitivity reaction

This is also called delayed type hypersensitivity in which a slow erythematous indurated lesion develops after an intradermally injected tuberculin (or similar antigen) on an individual.

Stimulatory hypersensitivity

Thyroid cells are normally stimulated by TSH through a membrane associated receptor. The long acting thyroid stimulator (LATS) which is an antibody against some components if the receptor also produces TSH like activity but it is more prolonged. The continued stimulation of LATS leads to hyperthyroidism. Similarly, anti-lymphocyte globulin is stimulatory to lymphocytes in appropriate conditions.

Type VI: Antibody dependent cell-mediated cytotoxic mechanism (ADCC)

This mechanism does not require complement activity. The effector cells are neither T nor B cells but are called K cells. The specificity of this reaction resides in the antibody molecule. Only very small amounts of antibody are required to produce this reaction and therefore this mechanism is effective in areas where antibody concentration may be minimal, e.g, at the site of solid tumors. The full significance of this mechanism has not been known.