Neuvenge
Encyclopedia
Neuvenge, Lapuleucel-T is a therapeutic cancer vaccine
(TCV) in development (clinical trial
) by Dendreon
(DNDN). It uses the "immunotherapy
platform approach" first successfully demonstrated on the U.S. Food and Drug Administration
(FDA)-approved TCV Provenge. It was first tested on breast cancer
patients with tumors expressing HER2/neu
, and is now scheduled to be tested on bladder cancer
patients.
are still available outside of the US. The idea of harnessing the antigen presenting cells (APC)'s to recognize cancer and target tumor cells for apoptosis
(cell death) by the CD8
(cytotoxic cells) is a common approach to cancer vacine researchers.
This 1997 example article describes targeting EGFR
and other cell products and attaching their antigens to the CD64
receptor cells also using GM-CSF to grow more cells. The NIH calls this topic "Biological response modifiers (BRMs) occur naturally in the body and can be produced in the laboratory. BRMs alter the interaction between the body's immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the disease."
Immunocompromising diseases have caused many deaths in human history. An ongoing example is Karposi's sarcoma (KS) caused by the Human herpesvirus 8 virus normally controlled by the body's immune system. KS is normally a rare diseaae but AIDS
has made it all to commonplace. AIDS patients, whose immune system has been compromised, fall victim to serious opportunistic infections such as (TB
) and KS. The movie "Philadelphia (film)
" gives a dramatic representation of AIDS and KS. A good method of preventing some cancers is to stop the viruses that lead to them. This is known as prophylatic treatment.
The current cancer prophylactic vaccines are for HVB (hepatitus "B" virus), HPV (cervical cancer
, vaginal, vulvar cancer
, penile, anal cancer
) and HPV-positive oropharyngeal cancer
are all defenses utilizing immunotherapy against viruses that lead to cancer.
in Russia. DNDN's future will require a different skill set to manage the mass production
of this first-of-a-kind product. There are 32,000+/yr deaths from prostate cancer
(CaP) in the US and that is only those with metastatic CRPC. If most of these patients were to receive this product that would increase current 2,000 output 16X. When (If) the project is expanded to those whose CaP is still controlled by hormone therapy that number could easily quadruple for the US alone. Were this therapy to be used on ALL Prostate cancer patients as a monotherapy that's (120,000+/yr.in the US). If those who are still on hormone therapy the numbers are in the millions. There are currently 2,000,000+ CaP patients in the US.
DNDN is busy building plants, which all require FDA approval, in Morris Plains, New Jersey
, Atlanta, Georgia
and (Los Angeles County, California
area) Seal Beach, California
(actually in Orange County, California
) for large scale Provenge production. They are still seeking overseas partners for development offshore.
In a change of course, DNDN is planning a bladder cancer clinical trial using Neuvenge to begin 2011.
DNDN is also using ACI technology Active cellular immunotherapy "This is a therapuetic platform using the patient's own cells to simulate an immune response." These are two major candidates:
Cancer vaccine
The term cancer vaccine refers to a vaccine that either prevents infections with cancer-causing viruses, treats existing cancer or prevents the development of cancer in certain high risk individuals...
(TCV) in development (clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
) by Dendreon
Dendreon
Dendreon is a Seattle based biotechnology company. Its lead product, Provenge , is an immunotherapy for prostate cancer...
(DNDN). It uses the "immunotherapy
Immunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
platform approach" first successfully demonstrated on the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA)-approved TCV Provenge. It was first tested on breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
patients with tumors expressing HER2/neu
HER2/neu
HER-2 also known as proto-oncogene Neu, receptor tyrosine-protein kinase erbB-2, CD340 or p185 is an enzyme that in humans is encoded by the ERBB2 gene. Over expression of this gene is correlated with higher aggressiveness in breast cancers...
, and is now scheduled to be tested on bladder cancer
Bladder cancer
Bladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...
patients.
History
The concept of immunotherapy for cancer has been known for hundreds of years and was used by Dr William Coley et al. in the 1800s. Coley's ToxinsColey's Toxins
Coley's toxins is a mixture consisting of killed bacteria of species Streptococcus pyogenes and Serratia marcescens, named after William Coley, a surgical oncologist who developed the mixture in the late 19th century as a treatment for cancer.- History :Observations of...
are still available outside of the US. The idea of harnessing the antigen presenting cells (APC)'s to recognize cancer and target tumor cells for apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
(cell death) by the CD8
CD8
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
(cytotoxic cells) is a common approach to cancer vacine researchers.
This 1997 example article describes targeting EGFR
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
and other cell products and attaching their antigens to the CD64
CD64 (biology)
CD64 is a type of integral membrane glycoprotein known as an Fc receptor that binds monomeric IgG-type antibodies with high affinity. It is more commonly known as Fc-gamma receptor 1...
receptor cells also using GM-CSF to grow more cells. The NIH calls this topic "Biological response modifiers (BRMs) occur naturally in the body and can be produced in the laboratory. BRMs alter the interaction between the body's immune defenses and cancer cells to boost, direct, or restore the body's ability to fight the disease."
Immunocompromising diseases have caused many deaths in human history. An ongoing example is Karposi's sarcoma (KS) caused by the Human herpesvirus 8 virus normally controlled by the body's immune system. KS is normally a rare diseaae but AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
has made it all to commonplace. AIDS patients, whose immune system has been compromised, fall victim to serious opportunistic infections such as (TB
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
) and KS. The movie "Philadelphia (film)
Philadelphia (film)
Philadelphia is a 1993 American drama film that was one of the first mainstream Hollywood films to acknowledge HIV/AIDS, homosexuality and homophobia. It was written by Ron Nyswaner and directed by Jonathan Demme. The film stars Tom Hanks and Denzel Washington...
" gives a dramatic representation of AIDS and KS. A good method of preventing some cancers is to stop the viruses that lead to them. This is known as prophylatic treatment.
The current cancer prophylactic vaccines are for HVB (hepatitus "B" virus), HPV (cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
, vaginal, vulvar cancer
Vulvar cancer
Vulvar cancer, a malignant invasive growth in the vulva, accounts for about 4 % of all gynecological cancers and typically affects women in later life. It is estimated that in the United States in 2006 about 3,740 new cases will be diagnosed and about 880 women will die as a result of vulvar cancer...
, penile, anal cancer
Anal cancer
Anal cancer is a type of cancer which arises from the anus, the distal orifice of the gastrointestinal tract. It is a distinct entity from the more common colorectal cancer. The etiology, risk factors, clinical progression, staging, and treatment are all different. Anal cancer is typically a...
) and HPV-positive oropharyngeal cancer
HPV-positive oropharyngeal cancer
Human papillomavirus -positive oropharyngeal cancer also known as HPV16+ oropharyngeal cancer or HPV+ OPC is a recognized subtype of Oropharyngeal squamous cell carcinomas , associated with the HPV type 16 virus.-Causes:...
are all defenses utilizing immunotherapy against viruses that lead to cancer.
Milestones
"A successful (TCV) is considered a milestone for cancer immunotherapy." The only approved TCVs, as of 2010, are Provenge in the US and OncogeneOncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
in Russia. DNDN's future will require a different skill set to manage the mass production
Mass production
Mass production is the production of large amounts of standardized products, including and especially on assembly lines...
of this first-of-a-kind product. There are 32,000+/yr deaths from prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
(CaP) in the US and that is only those with metastatic CRPC. If most of these patients were to receive this product that would increase current 2,000 output 16X. When (If) the project is expanded to those whose CaP is still controlled by hormone therapy that number could easily quadruple for the US alone. Were this therapy to be used on ALL Prostate cancer patients as a monotherapy that's (120,000+/yr.in the US). If those who are still on hormone therapy the numbers are in the millions. There are currently 2,000,000+ CaP patients in the US.
DNDN is busy building plants, which all require FDA approval, in Morris Plains, New Jersey
Morris Plains, New Jersey
Morris Plains, billing itself "the Community of Caring," is a Borough in Morris County, New Jersey, United States. As of the United States 2000 Census, the borough population was 5,236....
, Atlanta, Georgia
Atlanta, Georgia
Atlanta is the capital and most populous city in the U.S. state of Georgia. According to the 2010 census, Atlanta's population is 420,003. Atlanta is the cultural and economic center of the Atlanta metropolitan area, which is home to 5,268,860 people and is the ninth largest metropolitan area in...
and (Los Angeles County, California
Los Angeles County, California
Los Angeles County is a county in the U.S. state of California. As of 2010 U.S. Census, the county had a population of 9,818,605, making it the most populous county in the United States. Los Angeles County alone is more populous than 42 individual U.S. states...
area) Seal Beach, California
Seal Beach, California
-Neighborhoods:Seal Beach encompasses the Leisure World retirement gated community with roughly 9,000 residents. This was the first major planned retirement community of its type in the U.S...
(actually in Orange County, California
Orange County, California
Orange County is a county in the U.S. state of California. Its county seat is Santa Ana. As of the 2010 census, its population was 3,010,232, up from 2,846,293 at the 2000 census, making it the third most populous county in California, behind Los Angeles County and San Diego County...
) for large scale Provenge production. They are still seeking overseas partners for development offshore.
Prospects
DNDN have stated that their therapy is not a one-hit wonder and they plan to "move forward one Provenge-like new cancer treatment every year". This will demonstrate that they really have an immunotherapy platform approach to cancer.Combinational therapy
Involves using:- Primary care
- surgery
- radiation
- AdjuvantAdjuvantAn adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
care- hormone deprevation for those cancers effected by sex steroids
- chemotherapyChemotherapyChemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
- therapeutic vaccine therapy. Immunotherapy has added another tool or leg for Oncologist to fight cancer. This therapy could be a part of all the other therapys listed.
Neuvenge history
Neuvenge is still in preliminary clinical trials and is evolving as of 2011. First Neuvenge trials were performed on patients with metastatic breast, ovarian or colorectal cancer that expressed HER-2 (HER2/neu). Some patients with stable disease after week 48 received an additional "booster" treatment using the identical protocol. Lapuleucel-T is an investigational active immunotherapy product consisting of autologous peripheral blood mononuclear cells, including antigen presenting cells, which are cultured ex vivo with BA7072, a recombinant fusion antigen consisting of portions of the intracellular and extracellular regions of HER-2/neu linked to granulocyte-macrophage colony-stimulating factor.In a change of course, DNDN is planning a bladder cancer clinical trial using Neuvenge to begin 2011.
DNDN is also using ACI technology Active cellular immunotherapy "This is a therapuetic platform using the patient's own cells to simulate an immune response." These are two major candidates:
- Carbonic anhydrase IX (CA9) for kidney, colon, cervical cancers
- Carcinoembryonic antigen (CEA) for breast, lung and colon cancers