Immunotherapy of cancers

Cancer Vaccines
Cancer vaccines are an emerging type of biological therapy that is still experimental. At this time, the FDA has not approved any cancer vaccines for use as a standard treatment, but many vaccines are now being tested against a variety of cancer types in ongoing clinical trials.

How to find current cancer vaccine clinical trials? What types of vaccines are being tested? OR when a vaccine might be appropriate for you?
The answers to these questions you can find in the following web site:

http://www.cancer.gov/clinicaltrials/learning/cancervaccines

Below are illustrated some of the most practical cancer vaccines which are currently located in different phases of clinical tests:

A cancer vaccine Onyvax (a monoclonal antibody 105AD7 anti-idiotype vaccine) is under going clinical trails in the St. George's Hospital, London, UK from 25 April 2002 for the treatment of advanced colorectal adenocarcinoma. The vaccine is administered endermic together with the BCG vaccine OR intramuscularly together with the alum adjuvant

Cancer VAX (a polyvalent melanoma vaccine) is being used together with the surgical treatment in the treatment of melanoma III stage from 17 February 2000 in three different centers of Australia (Breast Cancer Institute, Westmead, New South Wales; Royal Prince Alfred Hospital, Sydney, New South Wales; Royal Adelaide Hospital, Adelaide, South Australia), France (Pitie-Salpetriere, Paris), Israel (Tel-Aviv Medical Center, Tel-Aviv), Italy (Istituto Nazionale dei Tumori, Naples) and 25 centers of USA. In order to increase the cellular immune response, this vaccine is given together with the BCG-vaccine.

From 1 March 2001 in the University of Texas, USA for the treatment of patients with II-IV stage cancers of the Gastrointestinal Tract (esophagus, stomach, pancreas, big intestine) which contain cells with carcinoembryonic antigen (CEA) on their membranes, use the beginning part of peptide fragments of this antigen containing 7 amino acids (carcinoembryonic antigen peptide 1-6D). GM-CSF is also injected in addition to this peptide. (NLM Identifier http://clinicaltrials.gov/show/NCT00012246).

From 8 March 2001 in 3 clinical centers of USA: Washington Hospital Center, Lehigh Valley Hospital and Inova Fairfax Hospital an autologous tumor cell vaccine is under clinical tests for the patients with II and III stage adenocarcinoma of colon to prevent relapses after surgical treatments. (NLM Identifier http://clinicaltrials.gov/show/NCT00016133).

From 2 April 2001 in USA: Herbert Irving Comprehensive Cancer Center, New York use NY-ESO-1 peptide vaccine, endermic in the treatment of II-IV stage sarcoma of soft tissues expressing NY-ESO-1, LAGE antigen NY-ESO-1 or LAGE antigen. Granulocyte-macrophage colony stimulating factor (GM-CSF) is injected, subcutaneous, in additional to this vaccine. GM-CSF is injected 5 days continuously starting from 2 days earlier to the vaccine administration. (NLM Identifier http://clinicaltrials.gov/show/NCT00027911).

From 8 November 2001 in USA: Hoag Memorial Hospital Presbyterian, Newport Beach, California a vaccinotherapy is being practiced using autologous dendrite cells, autologous tumor cells and GM-CSF for the treatments of cancer patients with relapses of the III-IV stage kidney cancers. (NLM Identifier http://clinicaltrials.gov/show/NCT00014131).

From 9 November 2001 in USA: University of Chicago Cancer Research Center use vaccine developed on the basis of the prostate specific membrane antigen (PSA) to treat the Metastatic Hormone-Refractory Prostate Cancer (NLM Identifier http://clinicaltrials.gov/show/NCT00015977).
Beside this, IL-12 is injected in order to suppress the angiogenesis in the metastatic sites.
"Phase II Study of Immunization With Prostate-Specific Membrane Antigen-Pulsed Autologous Peripheral Blood Mononuclear Cells and Interleukin-12 in Patients With Metastatic Hormone-Refractory Prostate Cancer."

From 8 February 2002 in 20 different clinical centers of Canada and in 250 centers of USA the monoclonal antibody 11D10 anti-idiotype vaccine and monoclonal antibody 3H1 anti-idiotype vaccine are being used in the treatment of the patients with stage II or IIIA non-small cell lung cancer (T1-3, N1-2, M0). The vaccine is administered starting from the 14-45 days after operation. It is injected endermic, once a week for three weeks, and then switched on to the back up course- once a month for 2 years. Beside this, after the third injections of the vaccine the patients receive radiotherapy- 5 days a week for 5-6 weeks. (NLM Identifier http://clinicaltrials.gov/show/NCT00006470).

From 27 February 2002 in USA: Norris Comprehensive Cancer Center and Hospital, Los Angeles, California for the treatment of the patients with IIB, IIC, III, or IV cutaneous melanoma OR stage III or IV ocular or mucosal melanoma is being practiced a vaccinotherapy using Tyrosinase, gp100, and MART-1 peptides together with the alum adjuvant. Interleukin-12 and the granulocyte-macrophage colony stimulating factor (GM-CSF) are also used beside the vaccine (NLM Identifier http://clinicaltrials.gov/show/NCT00031733).

ALVAC-CEA/B7.1, a deactivated strain of a virus, is ongoing clinical trial for the treatment of metastatic colorectal cancer in Los Angeles (USC/Norris Cancer Center) as well as New York, Washington, D.C., Philadelphia, Birmingham, Chicago, and Ontario, Canada. Virus antigens are identical to the antigens exhibited by colorectal tumors. Unlike its predecessors, this vaccine is being administered immediately upon diagnosis along with chemotherapy. Although the studies are currently in early stages, it appears that patients are tolerating the joint vaccine/chemotherapy regimen without any unusual side effects.

VG-1000 Vaccine is a specialized vaccine developed by Dr. Valentin I. Govallo, MD, PhD, which undermines the cancer cells defense mechanisms. This vaccine is most beneficial in treating carcinomas and melanomas, and it is also indicated for some sarcomas (cancers of muscle, bone, and connective tissue) and in leukemia. Patients recently subjected to chemotherapy or radiation respond more slowly to VG-1000 as they have a depressed immune system. However, patients who have had neither radiation nor chemotherapy respond favorably. Thus VG-1000 is clearly indicated as first-line treatment for persons with recently diagnosed cancers, as well as to help prevent recurrence. This treatment is now available at two specialized facilities in North America, The Immuno-Augmentative Clinic in Freeport, Grand Bahamas, and also CHIPSA's - Center for Integrative Medicine in Tijuana, Baja California, Mexico.

In Maryland (United States), is conducted Phase II clinical trial to study the effectiveness of Tricom vaccine therapy with or without samarium Sm 153 lexidronam pentasodium in Treating Patients With Prostate Cancer and Bone Metastases

The name "Tricom" is shorthand for a combination of three powerful co-stimulatory molecules - B7-1, ICAM, and LFA-3 - that enhance T-cell response. The first Phase I trial of sequential Tricom vaccines against cancer in humans shows safety and good response.

The world's 1st cancer vaccine is approved April 03, 2008. A biotech company Antigenics received approval from the Russian Ministry of Public Health to market the cancer vaccine Oncophage for some types of kidney cancer.
The vaccine, called HSPPC-96, or Oncophage®, is a heat-shock protein, a class of compounds that has shown activity as autologous therapy, which means that the therapeutic agent is derived from and tailored to the tumors of individual patients. The HSPPC-96 vaccine contains antigens extracted from melanoma. Some of these antigens, like MART-1 and gp100, are unique to melanoma; others are found in many types of cancer. In a study of a vaccine against metastatic melanoma, researchers from Italy and the United States report complete responses in two of 28 patients with measurable disease after surgery and long-lasting stable disease in three others.

The approval of the Antigenics cancer drug is the first for any cancer immunotherapy by any regulatory body in the world. It comes after the treatment didn't pass muster with the FDA, despite $425 million spent developing the treatment over 12 long years. Oncophage differs from preventative vaccines because it is supposed to treat an existing malignant condition, not prevent precursors to a cancer's development (by contrast, Gardasil helps prevent cervical cancer by providing protection from human papillomavirus, but it doesn't treat cervical cancer itself.)

To find out more current clinical trials for cancer, visit the website in the page

• NIH CancerTrials
• National Cancer Institute (NCI)
• Oncolink
• New guide to help you choose the right clinical trials. Featured in Time Magazine, NPR radio and Fox News

Related links:
Advances in Designing CANCER VACCINES
CANCER VACCINES AND GENE THERAPY CURRENT CLINICAL STATUS

In difference to the other kinds of immunotherapy, the targeted immunotherapy is capable to trigger specific and long-term anti tumor effect, which can possibly result into a complete cure, bearing no serious side effects.

The xeno-vaccinotherapy has obvious advantages over the other types of treatment options, which are based on the application of peptide tumoral antigens and application of auto- or allogenic cellular vaccine. First of all, the small structural difference between the xenogenic onco antigens and other human analogues make them (xenogenic structres) high immunogenic and enable them to trigger high immune responses in human beings. Secondly, these xenogenic onco antigens can stimulate the cellular (mainly) immunity. Thirdly, the non tumoral xenoantigens, expressed on the cell surfaces can cause unspecific stimulating (adjuvant) effect in the antitumoral immune reactions.

Immunotherapeutic Preparations

Cytokines (cellular hormones)
Cancer vaccines also often have added ingredients to help boost the immune response in general. One type of added ingredients are cytokines, chemical messengers that recruit other immune cells to the site of attack, and help killer T cells do their job. In some cases, cytokines are added to the cancer vaccine mixture, in other cases they are given separately.

Gamma interferon
Gamma interferon is a recombinant version of a substance naturally produced by cells in the body to help fight infections and tumors.

Clinical studies in patients using interferon-γ, have revealed a broad range of biological activities including the enhancement of the oxidative metabolism of tissue macrophages, enhancement of antibody - dependent cellular cytotoxicity (ADCC) and natural killer (NK) cell activity. Additionally, effects on Fc receptor expression on monocytes and major histocompatibility antigen expression have been noted.

ACTIMMUNE® - is approved by the FDA for the treatment of two disease states: chronic granulomatous disease, and severe, malignant osteopetrosis.

Interferon-gamma was registered for the indication Granulocytomatosis in 1992 under the trade name Imukin® .

Interleukin-2 (IL-2, Proleukin)
Interleukin-2 is a naturally occurring substance made by cells in our immune system. It primary function is to stimulate certain cells of the immune system (most commonly CD4+ cells, called "CD4 positive" cells) so that they could reproduce more vigorously.
Interleukin-2 has been approved by the FDA for the treatment of some types of cancer under trade name Proleukin.

Roncoleukin® is a drug formulation of recombinant human interleukin-2. It is manufactured by recombinant DNA technology using a genetically engineered strain of non-pathogenic baker yeast Saccharomyces cerevisiae that contains human gene interleukin-2 (IL-2).

Tumor Necrosis Factor alpha-1 (TNF alpha-1) is one of the important cytokines. The first ever-approved cytokine of this type released for clinical practice is Beromun (tasonermin) – a product of Boehringer Ingelheim Company.

The TNF-alpha1 selectively bonds with the blood vessels of tumors and finally destroys them.
From 1999 this drug has been used intravenously in certain
specially-equipped medical centers of Germany, UK and Netherlands as a preoperative adjuvant therapy
for sarcoma of soft tissues of limbs with the aim to prolong or prevent amputations; or as a
palliative treatments of non-operative cancers.

Colony-stimulating factors
NEUPOGEN® (Filgrastim) - A hematopoietic growth factor- the human granulocyte colony-stimulating factor (G-CSF).

Filgrastim and the other Amgen product Pegfilgrastim (trade name NEULASTA™) has the same mechanism of action. Pegfilgrastim has reduced renal clearance and prolonged persistence in vivo as compared to Filgrastim.

Leukine (sargramostim) - A yeast-derived granulocyte-macrophage colony stimulating factor (GM-CSF).
"It was originally licensed by the FDA in March, 1991 for use following autologous bone marrow transplantation (BMT) and was licensed in December 1991 to prevent death following BMT engraftment delay or failure. It has subsequently been licensed in September of 1995, to prevent early death from infection following induction chemotherapy for older subjects suffering from acute myelogenous leukemia (AML)." CenterWatch

GranocyteTM (Lenograstim) - A hematopoietic growth factor- the human granulocyte colony-stimulating factor (G-CSF).

Antibody Therapy

HERCEPTIN
HERCEPTIN (Trastuzumab) is a recombinant DNA-derived humanized monoclonal antibody that selectively binds with the human epidermal growth factor receptor to protein HER2.

Herceptin is FDA approved for first-line use in combination with paclitaxel for the treatment of HER2 protein overexpressing metastatic breast cancer in patients who have not received chemotherapy for their metastatic disease. Herceptin as a single agent is indicated for the treatment of HER2 protein overexpressing metastatic breast cancer in patients who have received one or more chemotherapy regimens for their metastatic disease.

For details visit: Herceptin® (Trastuzumab), http://www.her2status.com/frames.htm

San Francisco, CA (11/26/97) - The approval by the FDA of the first antibody-based therapy for cancer represents good news for some patients with non-Hodgkin's lymphoma (NHL), as well as a milestone in biotech drug development. The new compound, called Rituxan or rituximab, is a genetically-engineered monoclonal antibody that targets a receptor called CD20 found on some B-cells. The Rituxan antibody marks the B-cells for destruction by the immune system, after which new B-cells are generated by stem cells. Stem-cells and B-cells bearing antibodies are spared by Rituxan, since they lack the CD20 antigen. In a clinical trial conducted at 31 U.S. medical centers, 166 patients with NHL who had failed to respond to conventional treatment with radiation and chemotherapy received a series of four infusions of Rituxan. About half of the patients saw their tumors shrink by at least half, while six percent had a complete remission of disease.
First Monoclonal Cancer Therapeutic

Beeson Group Research is developing improved techniques for radiolabeled antibody treatments of lymphomas in collaboration with Irwin Bernstein at the Fred Hutchinson Cancer Research Center.

Antibody program at the University Medical School in Homburg/Saarland, Germany, focuses on the generation of biological active antibodies for the treatment of malignant diseases. Initially, Hodgkin's Lymphoma has been used as a model and researches established natural killer (NK) and T-cell activating bispecific antibodies (Bi-Mab) for the effective treatment of the disease. Up to now, scientific group performed two clinical trials in 31 Hodgkin's patients with the NK-cell activating Bi-Mab achieving an overall response rate of 30% in otherwise progressive patients."So far, we have generated antibodies with specificity for the FAP antigen for the treatment of epithelial cancers, G250 antigen for renal cancer and CD30 antigen for Hodgkin's lymphoma."

Other related information in the Internet: Monoclonal Basics

Other Bio (Alternative) Cancer Therapies

Angiostatic Approach to Cancer Therapy (anti-angiogenic therapy)

The angiostatic approach to cancer therapy has proved that various inhibitors of angiogenesis can significantly control the tumor growths. By this time there are already more than 20 different inhibitors (drugs that block matrix breakdown; drugs that inhibit endothelial cells directly; grugs that block activators of angiogenesis; grugs that inhibit endothelial-specific integrin/survival signaling) of angiogenesis are under investigation in patients with advanced cancer.

To download a full version of the table illustrating - Angiostatic Approach to Cancer Therapy.

To find out more about angiogenesis-based medicines visit:

The WWW Virtual Library of Cell Biology - Angiogenesis - for an excellent collection of reviewed links in all levels.
The Angiogenesis foundation
Angiogenesis Research Industries, Inc.

ALOE VERA
"Aloe turns on the immune system by activating macrophages (white blood cells which “swallow” antigens), causing the release of immune-activating (and anti-cancer) substances such as interferons, interleukines, and tumor necrosis factor." Thus, aloe may help to prolong survival time and stimulate the immune system of cancer patients, according to recent research.

LAETRILE
"It has been known for over 35 years that Laetrile (also called Vitamin B17) has a very profound effect on many types of cancer cells."

Methylgloxal
"A cancer drug that works by starving the cancer cells of ATP (adenosine-5-triphosphate). Cancer cells need lots of ATP to survive and Methylglyoxal helps by reducing ATP levels, literally starving cancer to death!"

UKRAIN®
"Has maligno-toxic properties meaning that it selectively kills or inhibits the growth of all major types of cancer cells while being non-toxic with regard to normal cells. This is being achieved by the drug's ability to stop oxygen consumption only in malignant cells. Ukrain directly targets and kills cancer cells while at the same time, fortifying the immune system."
http://www.ukrin.com/ukrainindex.htm

Entelev/Cancell
Entelev works by inhibiting respiration of the cancer cells and thereby pushing the cancer cells into a more “primitive” stage. Once the cancer cells have been pushed into this primitive stage, the body can attack and dispose of them as it would any other foreign object. Cancell seems to work much the same as Ukrain in that it effects the cancer cell’s respiration and causes it to die.

GRAVIOLA
"In more than 20 laboratory tests, Graviola has been shown to target and kill malignant cells in 12 types of cancer including pancreatic, colon, breast, and lung cancer. Graviola has also been shown to be 10,000 times more powerful in killing colon cancer cells than Adriamycin."

Polyoxidonium

Polyoxidonium is a high-molecular weight physiologically active compound with pronounced immunomodulating activity, an N-oxidized polyethylene–piperazine derivative. The analysis of immunomodulating effect produced by Polyoxidonium proved its stimulating activity on some cytokines production in vitro, e.g. interleukin 1β (IL-1β), tumor necrosis factor (TNF)-α and IL-6. A dose-dependent increase in the intracellular killing by blood phagocytes was established under the action of Polyoxidonium.

Mistletoe

Extracts of mistletoe ( also known as Iscador / Viscumalbum / Plenosol / Helixor / Iscucin) are the most commonly used adjuvant to conventional cancer treatments in both Germany and Switzerland. Perhaps the most extensively researched alternative therapy, with a number of clinical trials and many hundreds of case reports, mistletoe extracts have demonstrated substantial benefit for patients with a variety of cancers.

Sodium dichloroacetate (DCA)

DCA is a drug that was recently found to induce the death of human breast, lung and brain cancer cells that were implanted into rats, while being non-toxic to healthy cells. This research was published in Cancer Cell, 11, 37–51, January 2007. DCA has been found to kill cancer cells by a newly discovered mechanism that appears to be common to several types of cancer. DCA, worked to reactivate the apoptosis mechanism of cancer cells, causing rapid shrinkage of tumors in rats. Mitochondrial reactivation represents an entirely new approach to treating cancer. DCA is different from other drugs that undergo clinical trials because it is not a “new” drug. It has already been used for decades in humans, and has a relatively safe profile. A DCA clinical trial has been announced in Alberta. It will examine the effects of DCA on a type of brain tumour.

The following clinics are offer DCA therapy

Medicor Cancer Centres in Toronto
The Chipsa Clinic in Mexico.

Polyatomic Oxygen Therapy
Cancer cells cannot live in a high oxygen environment. Polyatomic Oxygen Therapy is used to super-saturate the entire body with oxygen and in the process, purifies the whole body including the blood circulatory system (the lymph fluids and all internal organs). In this process of super-saturating the body with oxygen, it kills different types of cancer cells and at the same time gives the immune system a huge boost with no toxic side effects.

COMBINING TREATMENTS

All the supplements fall into two categories of biochemical mechanisms: some directly target and kill malignant cells while others work by super-charging the immune system and in some cases even acting to teach the immune system to recognize cancer cells. With supplements from both categories available, it makes a lot of sense to use a supplement that targets and kills cancer cells along with one that enhances the immunity. Most Holistic Health Care practitioners agree that your chances of curing cancer using a combination protocol with supplements from each category will be much more effective as compared to using supplements from each protocol on it's own.

What Is Holistic Medicine?
http://www.holisticmed.com/whatis.html

Here are some of the clinics which offer this type of cancer therapy.

Links to Alternative Medicine Practitioners, Clinics and Resources for Cancer Treatment: http://www.heall.com/body/resource/organizations/cancer.html
http://www.heall.com/body/askthedoctor/disease/cancer/resources.html
http://www.heall.com/links/complementarymedicine.html

Cancer Cure Foundation:
http://www.cancure.org/directory.htm The site includes List of Clinics in the United States, List of Clinicsoutside the United States, except Mexico and the Mexican Clinics.

Here are some of the popular clinics with links to write ups on each clinic:
Providence Pacific Hospital, South America
Dr. Kurt Donsbach's Hospital Santa Monica, Mexico
HUFELAND CLINIC For Holistic Immunotherapy, Germany
Immuno-Technologies Cancer Clinic (ITL), Freeport, Bahamas

A Botanical Approach to the Treatment of Cancer - Online article by Dr. Michael Tierra L.AC., O.M.D. Here you can read about: Apoptosis vs. Necrosis, Angiogenesis, The Holistic Treatment of Cancer, Diet for Cancer Patients, Dr. Miriam Lee’s Bean Soup Treatment for Cancer, Soybean Extract: Special Nutrition for Cancer Patients and a wide range of Herbal Treatment.
http://www.planetherbs.com/articles/

Other clinics, Resources & Links for alternative cancer therapy.

• A good Reviews of Alternative Therapiewhere you can find:
  • Herbal/ Plant Therapies:
    Aloe, Cat's Claw, Coriolus Versicolor (mushroom), Essiac, Garlic, Green Tea, Hoxsey, Mistletoe, Saw Palmetto, Traditional Chinese Medicine.
  • Biologic/Organic Therapies:
    Cartilage, Coenzyme Q10, Coley Toxins, Govallo Embryo therapy, Homeopathy, Immune Augmentation Therapy, Melatonin, Modified Citrus Pectin, MTH-68, Selenium.
• People Against Cancer, alternative cancer treatments
• The Gerson Institute - http://www.gerson.org/
• The Cancer Cure Foundation "A non-profit organization providing information on alternative cancer therapies, including referrals, since 1976."
• Complementary/Integrative Medicine Education Resources

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