What is cancer?

Cancer is a large group of diseases characterized by continual generation of abnormal cells or neoplasm that have lost their genetic or genomic stability. These unstable genetic mutations in cancer cell genomes lead to uncontrollable cancer cell division, growth, invasion, escape from immune screening and metastasis. Thus, cancers are not only localized genetic diseases but also systemic immune deficient diseases.

The major challenges for anti-cancer product development are genomic instability, heterogeneous population of cancerous cells including pre-cancer cells, mature cancer cells and cancer stem cells that continue to mutate and survive under extreme conditions, have too many chromosomes in one cancer cell with over-expression of thousands of genes including many onco-genes, have multiple growth pathways, form solid-tumors, metastasize, suppress the immune system, and transform to cancer stem cells that tolerate anti-cancer drugs. The minor challenges are the misleading results obtained from in vitro cancer cell lines and animal models in nude mice, nude rats, knockout mice, knockout rats. For example, a nude mouse will allow human cancer cells to grow in its body due to its deficiency in T-cells. Anything that promotes the production of T-cells in the nude mouse will have effect on killing human cancer cells. However, in human, the cause of cancer is not due to T-cell deficiency and those factors that induce the production of T-cells in nude mouse may not have effect in killing human cancer cells in human body. Another example is using the knockout mouse or rat to conduct anticancer drug screening, if the knockout gene is p-53 or p-73, anything which repairs p-53 or p-73 will be effective. However, cancer cells may have losses other than p-53 and or p-73. In this case, the screening is not relevant at all.

Above all, the most challenging part is understanding the solid-tumor. How is it initiated and formed? What is the role of cancer stem cells in solid-tumor formation? Can cancer stem cells form solid tumor structure in vitro? What is the solid structure of the tumor? Is the solid structure of the tumor the same in vitro and in vivo? Is solid tumor an organ? ...

Why is cancer a large group of genetic diseases?

Cancer is a large group of genetic diseases because all cancer cells or tumor cells are genetically mutated with unstable genomes. These unstable genomes continue to mutate to generate a heterogeneous population of cancerous cells that may include pre-cancer cells, mature cancer cells and cancer stem cells to form solid tumors. Cancer stem cells are the result of ultimate mutation. Cancer stem cells can survive under extreme conditions such as exhausted or partially depleted O2, CO2 and nutrients, and in the presence of some apoptosis inducers and anticancer drugs. Thus, cancer or tumor cells are not a clone of cells or clones of cells. Cancer cell lines with mutant clones may mislead researchers using that material. Any idea, concept or therapy based on the clone concept will be susceptible to this weakness. Furthermore, cancer or tumor cells including cancer stem cells continue to mutate and in most cases cannot self renew due to unstable, non-symmetric genomes with multiple mutations in DNA sequence such as deletion, duplication, reversion, translocation and chromosomal copy number changes.

Why is cancer a large group of immune diseases?

Cancer is a large group of immune diseases because cancer or tumor cells' genetic mutations or antigenic material are not detected by the immune system and no measure is taken against them although they are "foreign" or "illegal" genetically. The immune system regards a cancer or tumor cell as "self" since the cancer or the tumor cell expresses self-recognition molecular patterns. These patterns, including major histocompatibility complex (MHC) molecules, are self-recognition passwords or symbols that prevent the immune system from attacking its own cells. Cancer cells that express self-recognition molecular patterns can survive immune screening when they grow, invade and metastasize. However, cancer cells that do not express self-recognition molecular patterns may also survive if they are not exposed to immune screening such as those located inside a solid tumor where immune screening cells cannot access. That is to say that the solid tumor organ may express self-recognition molecular patterns on the surface to protect internal cells that do not express such patterns. Therefore, immunotherapy by lymphocytes including T-cells and dendritic cells may have some effect in shrinking the tumor by killing cancer cells that do not express self-recognition molecular patterns or expressing antigenic material that can be recognized as foreign.

What causes cancer?

Any agent that can mutate a DNA sequence may cause cancer. Natural agents, including carcinogenic chemicals such as high concentrations of nitrogen peroxide, low concentration of many chemotherapy drugs that fragment DNA, free radicals or strong oxidants, radioactive material, heavy metals, radiations, viruses, and some bacteria that mutate DNA may eventually cause cancer. These agents usually facilitate DNA sequence mutations by DNA sequence deletion, duplication, reversion, translocation and chromosomal copy number changes.

That three events happen at the same time is required for cancerous cells to initiate: at least one of over 50 onco-genes (such as c-myc) is turned on, at least one of several tumor-suppressor genes (such as p-53 and p-73) loses its activity and these mutations are not detected by the immune system. Pre-cancer and inherited high-risk individuals have a higher possibility of getting cancer than others since they have a high possibility of carrying pre-cancer cells that may have oncogene expression or loss of tumor suppressor genes. Cancer may be prevented by true cancer vaccines that induce pre-cancer and cancer cell specific immune responses including polyclonal antibodies to kill them.

BioMedicure has developed next generation of products in CancerVaccine™ to prevent cancer. CancerVaccine™ are harmless derivatives or variants of cancer cells. CancerVaccine™ induce immune responses against abnormal or mutated cells including pre-cancer cells, mature cancer cells and cancer stem cells for acquired immunity. The coverage of the immunity against specific genetic mutations is built in CancerVaccine™. Thus, CancerVaccine™ target genetic mutations that may lead to cancer initiation, formation and development. CancerVaccine™ induce acquired or adaptive immune responses against genetic mutations to prevent cancer.

CancerVaccine™ is revolutionary because these products are true cancer vaccines that will induce immune responses against genetic mutations or antigenic material in cancer cells specifically. Thus, CancerVaccine™ can be used for cancer prevention, cancer control and treatment through CancerVaccine™ induced immune responses including cancer-cell-specific-polyclonal-antibodies or AntiCancerBody™.

What is a malignant solid-tumor?

A malignant solid tumor is an organ consisting of mostly cancer cells with a unique structure where most cancer cells on the outside layers are actively dividing, growing and escaping from immune screening while cancer cells inside initially grow rapidly then slow down due to limited space, oxygen and nutrition. Those cells in the middle of a solid tumor organ eventually die or go dormant in the hypoxic environment. The structure of a solid-tumor is the major challenge for anti-cancer product development since it links all cancer cells together to form an organized solid tissue or organ. The majority of anticancer products may work well at molecular or cellular levels against cancer cell lines, but not at the organ level or systemic level against a solid-tumor organ. The solid structure of a solid tumor organ and cancer stem cells within a solid tumor are major challenges anti-cancer drugs face. BioMedicure's next generation of products in enriched cancer stem cells, or CancerStemCell™, addresses these challenges since CancerStemCell™ products are tumorigenic and form solid structure in vitro and have other features, such as heterogeneous, randomly mutating and survive under extreme conditions and resistant to apoptosis inducers, cancer cell lines do not have.

Why is a solid tumor an organ?

A solid tumor has a unique structure at molecular, cellular, organ and body system levels. At the molecular level, a solid-tumor attracts nutrients for growth and drives away other things including immune screening cells that would normally hinder the growth. At the cellular level, a solid-tumor is composed of constantly mutating cancer cells, and actively dividing normal cells. Most, if not all, cancer cells are networked together by their solid structure of intratumoral, extracellular and cell membrane proteins. Normal cells within the solid tumor may be loosely connected each other due to their lower level of gene expression. At the organ level, a solid tumor is an organ because it is organized by cancer cells through a solid structure which expands forcefully and irregularly in multiple directions. The main tissue of the tumor organ is the solid-structure network of mostly cancer cells and sporadic tissue composed of actively-dividing normal cells and blood vessels. BioMedicure has developed Tumorase™ to destroy the solid-structure of the tumor and kill cancer cells including cancer stem cells locally and in vitro as well. BioMedicure's next generation of products in enriched cancer stem cells, or CancerStemCell™, are not only tumorigenic in vitro without the aid of any matrix gel or growth factor supplement but also form solid structure for a tumor and have mutations or antigenic material comparable to that of a solid tumor in vivo.

What are metastasized cancer cells?

Metastasized cancer cells are cancer cells that have migrated away from its tumor primary site with the tolerance of the immune system. These cancer cells are usually characterized by their expression or over-expression of self-recognition molecular patterns for lymphocytes including major histocompatibility complex II (MHC II). Thus, the immune system will not restrict these cancer cells’ movement in the body since they may have both local tissue self-recognition molecular patterns (MHC I) and lymphocyte self-recognition molecular patterns (MHC II). Metastasized tumors are detrimental since they grow very fast and can exhaust a patient’s nutrients in a short period of time to starve the patient to death.

Why doesn't an immune system attack cancer cells?

Most, if not all, cancer or tumor cells have self-recognition "passwords" that not only pass the antigen screening process but also interfere with the antigen comparison processes and hide their antigenic material. Thus, cancer cells' genetic mutation information in antigenic material is not recognized by the immune system. The solid structure of the tumor also traps immune components including macrophages. The self-recognition "passwords" are self-recognition molecular patterns including MHC I and MHC II. Cancer cells with low expression or over-expression of MHC I without antigens bind to it can grow at the originating place to usually form a tumor. Cancer cells expressing or over-expressing MHC II can travel around the body for metastasis. Blood cancer is a metastatic cancer but may not form local tumors if they do not express MHC I. In order for a body's immune system to recognize cancer cells, the immune system needs to be genetically engineered or re-built with CancerVaccine™ so the immune system's detection method and sensitivity for cancer cells are greatly enhanced by cancer cell specific immune responses including polyclonal antibodies. After the vaccination, the immune system will be able to detect pre-cancer cells, cancer cells and cancer stem cells and systematically kill all of them for extended time.

What is a true cancer vaccine?

A true cancer vaccine is and should be a product that can not only prevent cancer but can also be used for cancer treatment if a cancer patient's immune system is intact. Thus, the true cancer vaccine will induce immune responses against cancerous cells specifically for a long time by acquired or adaptive immune responses against pre-cancer cells, cancer cells and even cancer stem cells. Therefore, virus vaccines, non-specific immune stimulants, mono- or polyclonal antibodies and immunotherapy lymphocytes including modified T-cells and dendritic cells are not really true cancer vaccines since they do not and cannot induce immune responses against cancer or tumor cells specifically.

What is an immune system?

An immune system is a body's organization (both structural and functional) that maintains the integrity of the body genetically and immunologically against any foreign attacks by pathogens, injuries, or the body’s own mutation(s) through the blood and lymph systems. In the immune system, there are multiple layers of defenses and offenses synergistically initiated, coordinated and regulated by all components of the immune system. The components of the immune system are very diversified ranging from non-biological physical barriers or structures and biological or functional actives that are either non-cellular or cellular. The non-cellular bioactives may include various serum antibodies, interleukins, cytokines and others. The cellular bioactives are major lymphocytes or white blood cells. The physical barriers, non-cellular actives and lymphocytes are coordinated, regulated and maintained synergistically for the health of the body. In addition to defend the body against foreign invasions and internal trash clean-up and disposal, the immune system also fights against cancer to maintain a body's genetic integrity. Through evolution, the body acquired abilities to keep all cells "self" genetically by antigen presentation processes, which is destructive and very complicated but has a memory capacity up to 109. However, via adaption, the immune system uses a non-destructive system to easily recognize "self" and foreign by their cell surface molecular patterns. For example, lymphocytes including macrophages and dendritic cells recognize cells with major histocompability complex II or "MHC I" molecules as stationary or non-mobile "self, or friend" and recognize cells with major histocompability complex I or "MHC II" molecules as non-stationary or mobile "self or friend" and will not check other things inside the cell which can be foreign. This is one of the few ways cancer cells may escape the immune screening process where cancer cells are not searched thoroughly since there is no reason to do so. When BioMedicure's CancerVaccine™ is used for vaccination, the immune system finds that the vaccine are not "self or friend" and go through the destructive antigen presentation processes. The immune system finds out that there are many "threatening" antigens and memorize them by B-memory cells, T-memory cells and induce plasma cells to secrete polyclonal antibodies that can bind to the antigenic material specifically. The smart immune system may use the newly acquired antigens information to search and destroy cancerous cells that have such antigenic material. Although they have "self or friend" recognition molecular patterns on their cell surfaces. The CancerVaccine™ induced immune responses are very powerful since cancer cell specific immune responses including polyclonal antibodies can detect cancer cell specific antigenic material hidden in cell membranes or inside the cell.

What is innate immunity?

Innate immunity is a body's quick immune response against "foreign" pathogens performed by neutrophils, eosinophils, basophils, mast cells, monocytes, macrophages, natural killer cells and platelets. The immune system will treat cancer cells from different species as "foreign" and launch innate immune responses against them within 4-6 hours since their self recognition molecules are different.

What is humoral immunity?

Humoral, adaptive or acquired immunity refers to the immune responses built in the immune system with long-lasting memory. Cancer prevention needs such immune responses that are also economic in addition to long lasting. BioMedicure's CancerVaccine™ can effectively induce such immune responses in wild-animal types.

What are antigen presentation processes?

Antigen presentation processes are very complicated and many parts are still unknown. Antigen presentation processes are performed by many cellular and non-cellular components. The cellular components include several different types of lymphocytes to acquire the antigen information in order to make immune responses to kill cells with antigenic material specifically for humoral immunity. An antigen presentation is usually begun with antigens bound to MHC I molecules and/or the sampling of professional antigen presenters including macrophages and dendritic cells to pick up the antigen or engulf and digest something foreign. They usually do not sample a whole cell with self-recognition molecular patterns including MHC I and/or MHC II on their cell surfaces even though they may have antigens inside the cell. However, when a cell is injured and the structure of the self-recognition molecular patterns change, the cell will be sampled and analyzed to see if any mutation is present. In this case, a macrophage or dendritic cell first engulfs the sampled cell and digests everything in or on the cell. Digested fragments will bind to MHC II molecules on the surface of macrophage or dendritic cells. With digested fragments on cell surfaces, macophages and dendritic cells will migrate to major lymph nodes to identify if digested fragments are antigens with the help of T-helper cells, B-cells and cytokines. A self-antigen is usually bound tightly to a T-cell with that specific antigen receptor and eliminated to avoid autoimmunity. An antigen is bound loosely to a T-cell with the help of T-helper cells and cytokines secreted by professional antigen presentors (i. e. dendritic cells and macrophages) to further the process to T-memory cells, B-memory cells and plasma cells that can secrete an antibody (thousands of the same per second) against the antigen, and the secondary antibody respnse. BioMedicure's CancerVaccine™ enhance antigen presentation processes to effectively induce pre-cancer, cancer and cancer stem cell specific immune respnses including polyclonal antibodies that in turn can kill up to 100% of all cancerous cells.

How is a tumor tolerated by the immune system?

From the immune point of view, cancer is a population of mutated cells that not only express onco-gene proteins, but also express self-recognition proteins. Furthermore, the solid tumor expresses chemokines and interleukins that drive away immune screening cells including T-cells, dendritic cells, monocytes, natural killer cells and B-cells. On the other hand, solid tumors express chemokines that attract and trap macrophages. Thus, genetic mutation evidence is never sampled, passed on or identified by the immune system since the antigen presentation processes are broken and the immune system is impaired.

In a specific cancer case, are cancer cells belonging to the same clone?

No. Although all cancer cells from the same tumor may derive from a single cancer cell originally, their genetic material (DNA) are not the same due to their unstable genomes. These unstable genomes cause random mutations under the immune screening pressure. Thus, in a tumor, cancer cells do not belong to the same clone. Furthermore, they do not belong to several clones either. However, cancer cell cultures tend to have clones or subclones of fixed mutants that are no longer tumorigenic, heterogeneous or mutating. The degree of heterogeneity or cloneness will depend on the passage of cancer cell lines. Due to many passages or subcultures with optimal medium while without immune restriction, fixed mutants can be the majority of the population that best adapted to the same medium, an artificial environment. B16 melanoma cancer cell line is a good example where only about 1-5% of the cells are tumorigenic, heterogeneous and mutating true cancer cells. BioMedicure uses proprietary processes to inactivate non-cancer stem cells and expand cancer stem cells to enrich cancer stem cells or CancerStemCell™. CancerStemCell™ products are tumorigenic, heterogeneous and randomly mutating cancer cells capable of surviving under extreme conditions including exhausted or partially depleted O2, CO2 and nutrients, and in the presence of some apoptosis inducers and anticancer drugs.

Why are current chemotherapy or immunotherapy drugs most effective in lymphoma or leukemia but not for other cancer types with solid tumors?

Lymphoma and leukemia cancer cells usually do not organize to form solid tumors and each individual cancer cell can be easily accessed and killed by chemotherapy drugs (within the physiological tolerance threshold). However, the dose that can kill solid tumor cancer cells usually exceed the physiological tolerance threshold due to the solid-structure of the tumor.