Avicine, tested and developed by AVI BioPharma, and also known as CTP-37 was trialled as a possible

cancer vaccine A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines ...

to treat a number of different

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

s. These included

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

and

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

. The treatment was trialled as and intended to be induced via

intramuscular injection Intramuscular injection, often abbreviated IM, is the medical injection, injection of a substance into a muscle. In medicine, it is one of several methods for parenteral, parenteral administration of medications. Intramuscular injection may be ...

into the bloodstream, the location dependent on the treatment area. Common

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s during

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s included

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

and

chills Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. It occurs during fever due to the release of cytokines and prostaglandins as part of the inflammatory ...

as experienced with many other conventional

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...

s. The vaccine operated by eliciting

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

against human chorionic gonadotropin (hCG) a cancer associated

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

expressed by most cancer cells, with the goal of prolonged survival for those affected. Avicine was originated by AVI BioPharma in the USA, who licensed the product to SuperGen. However, due to delays in clinical testing, as a result of research difficulties, the owners of Avicine were forced to direct their attention to other areas being the investigation and treatment of cardiovascular and infectious disease indications.

Medical Uses

Avicine never reached the commercial treatment phase as research was discontinued on 15 January 2007. The cancers Avicine was designed to manage were, pancreatic, colorectal and

. In a one-year, Phase II Avicine cancer vaccine study, a group of

patient A patient is any recipient of health care services that are performed by Health professional, healthcare professionals. The patient is most often Disease, ill or Major trauma, injured and in need of therapy, treatment by a physician, nurse, op ...

s were treated with Avicine alongside the combination of Gemcitabine (Gemzar), the results yielding that Avicine could be induced alongside Gemzar, in the

prostate The prostate is an male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemica ...

region. As the 3rd and 4th clinical trials were not done this was never done as a commercial treatment.

Contraindications and drug interactions

Patients who were

pregnant Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

were not to be treated by Avicine, as it elicits

against hCG, a cancer associated oncofoetal protein that is also prevalent during the development of a child in the

womb The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bi ...

. As of 2007, due to the discontinued state of Avicine research, drug interactions have not been studied.

Adverse Effects

Results from a multi-center phase II study in test subjects with metastatic colorectal cancer in USA exposed that of 64 patients some experienced

s and

. Overall, the

s were tolerated well by the patients. 69% (55 of the 73 patients).

Key Development Milestones

Colorectal Cancer

After successfully completing a Phases I and II trials for the use of Avicine in

, a phase III licensing trail began to investigate Avicine as a first line treatment for colorectal patients alongside

chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...

in January 2001. The trial was randomised where the patients would either receive Avicine in combination with chemotherapy or chemotherapy unaided. However, Phase III was discontinued as of 15 January 2007.

Pancreatic Cancer

A multi-centre Phase II clinical trial of Avicine was conducted by Avi Biopharma, including 55 patients in the US. The trial was conducted 10 patients with

saw positive results in a pilot phase II trial of Avicine. A plan was proposed to begin a phase III trial for patients with pancreatic cancer. However, in 2003 it was reported in order to do so an additional corporate partner was needed for the trial to be instigated. Research was discontinued on 15 January 2007 as an additional corporate partner was found and phase II was still not complete.

Prostate Cancer

A phase I trial of Avicine was completed by Avi Biopharma in patients with

, however after this stage research was discontinued on 15 January 2007.

Drug Properties and Chemical Synopsis

Route of administration In pharmacology and toxicology, a route of administration is the way by which a medication, drug, fluid, poison, or other substance is taken into the body. Routes of administration are generally classified by the location at which the substance ...

: IM

Formulation Formulation is a term used in various senses in various applications, both the material and the abstract or formal. Its fundamental meaning is the putting together of components in appropriate relationships or structures, according to a formula ...

: unspecified

Class Class, Classes, or The Class may refer to: Common uses not otherwise categorized * Class (biology), a taxonomic rank * Class (knowledge representation), a collection of individuals or objects * Class (philosophy), an analytical concept used d ...

Cancer Vaccines A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines ...

Mechanism of Action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical Drug interaction, interaction through which a Medication, drug substance produces its pharmacological effect. A mechanism of action usually includes mention o ...

Immunomodulator Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

;

Immunostimulant Immunostimulants, also known as immunostimulators, are substances (drugs and nutrients) that stimulate the immune system usually in a non-specific manner by inducing activation or increasing activity of any of its components. One notable example i ...

WHO ATC code: L03A-X (Other immunostimulants) EPhMRA code: L3A (Immunostimulating Agents Excluding Intereferons)

Chemistry of Avicine

The

chemical A chemical substance is a unique form of matter with constant chemical composition and characteristic properties. Chemical substances may take the form of a single element or chemical compounds. If two or more chemical substances can be combin ...

and

physical properties A physical property is any property of a physical system that is measurable. The changes in the physical properties of a system can be used to describe its changes between momentary states. A quantifiable physical property is called ''physical ...

of Avicine can be highlighted in the table below:

Pharmacology

Avicine (CTP-37) is a peptide fragment of Human chorionic gonadotropin (hCG), an oncofoetal protein expressed by most cancer lines, the significant role of hCG being to ward off the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

, the same way cells of the developing

foetus A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic stage, the fetal stage of development takes place. Prenatal development is a ...

ward off the immune system. In some studies expressions of hCG in colorectal cancer has been positively correlated with reduced survival rates. Two

epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although e ...

s can be found in CTP-37 one of which is dominant and can elicit anti-bodies against hCG. By employing this ideology Avi Biopharma created a modulated form of CTP-37 (Avicine) containing an extra peptide domain, more specifically denoted as a loop peptide. The modulation of the earlier formulation was done to force the immune system to act against multiple epitopes, with the aim of improving the survival rate of individuals with cancer. The moderated formula of Avicine was built on the basis of a study that indicated patients exhibited prolonged survival when they responded to more than one vaccine epitope. The majority of the world's population have been vaccinated against diphtheria use diphtheria toxoid (DT), and was therefore used a carrier protein due to the significant data available on its effects as a vaccine. Also, the established

immune response An immune response is a physiological reaction which occurs within an organism in the context of inflammation for the purpose of defending against exogenous factors. These include a wide variety of different toxins, viruses, intra- and extracellula ...

to DT was also believed to be important in encouraging an immune response to hCG peptides.

Therapeutic Trials

Colorectal Cancer

Phase I tests demonstrated a satisfactory safety profile of Avicine (CTP37-diphtheria toxoid/DT), whilst also establishing the immunological activity of the drug. In the following Phase II study 77 patients with colorectal cancer were treated with Avicine using Active Specialised Immunization (ASI), the CTP37-DT, prompting

in patients experiencing cancers that expressed very high hCG levels. The patients were given the vaccine at week 0, 4, 10 and 16. Of the 77 patients 56 of those produced antibodies to human chorionic gonadotrophin (hCG), in response to the vaccine. By

intention-to-treat analysis In medicine an intention-to-treat (ITT) analysis of the results of a randomized controlled trial is based on the initial treatment assignment and not on the treatment eventually received. ITT analysis is intended to avoid various misleading artifac ...

it was observed that of the vaccinated patients the

median The median of a set of numbers is the value separating the higher half from the lower half of a Sample (statistics), data sample, a statistical population, population, or a probability distribution. For a data set, it may be thought of as the “ ...

survival was 34 weeks. The median survival of patients who those who did not produce antibodies from the vaccine was 17 weeks, whilst the patients who developed antibodies from the vaccine exhibited a median survival of 42 weeks. Also, patients who developed median antibody levels (n=39) expressed higher survival rates than those who expressed antibody levels below the median value (n=38), where survival rates were 45 weeks and 24 weeks respectively (AVI BioPharma Inc.). Additionally, CTP-37 consists of two

s and those who responded to both epitopes demonstrated prolonged survival, with 65 weeks, compared to those who only reacted against one epitope who experienced a 39-week survival rate. Another randomised group was also given Pharmacia-Upjohn's Camptosar, where the subjects experienced a mean 35 weeks survival rate. Using this data AVI Biopharma formulated a new version of CTP-37 vaccine, which included another hCG peptide referred to as the loop peptide. Inclusion of the loop peptide is used primarily to modulate the dominance of the original substance, which would ideally force the immune system to react to the multiple epitopes, culminating with prolonged survival rates for colorectal cancer patients.

Pancreatic Cancer

patients were included in a study which confirmed treatment with Avicine produces comparable survival rates to treatment with Gemcitabine. A group was also tested with gemcitabine combined with Avicine, and expressed significantly better survival rates than those who were treated with either substance independently. Also, Gemcitabine did not affect the patients ability to have an immune response to Avicine's epitopes. Data from a phase Ib study including ten patients with pancreatic cancer established the safety and value of the use of Avicine in the subjects. The patients survived for periods greater than 6 months, which were historical survival rates for patients with metastatic pancreatic cancer. During the phase II study, one patient survived greater than 20 months, three lived more than 11 months, and 4 out of 6 patients remaining exceeded the 5.3 month period of median historical survival for this disease in 2001. The median survival in the 10 pancreatic patients was equal to 33 weeks with the Avicine (CTP-37) vaccine.

References

{{DEFAULTSORT:Avicine Vaccines Cancer vaccines Peptide vaccines