Northwest relies upon the contract manufacturing organization Cognate Bioservices for services supporting manufacture of its products for clinical trials. Their relationship with Cognate began before 2007, and is slated to extend through the first quarter of 2016.[1]:15 Due to cash flow issues common to development-stage companies, Northwest compensates Cognate through a combination of cash payments and stock.[1]:16 Cognate has also provided Northwest with at least one short-term loan, provided and paid in mid-2013.[1]:16As of 2014[update], Northwest's expanding clinical trials have led to an increased reliance on Cognate's services, and subsequent renegotiation of their agreement.[1][3]
Technology
The DCVax technology upon which NWBO's therapies rely involves injecting cancer patients with dendritic cells which have been harvested from them by leukapheresis (i.e. they are "autologous") and activated by incubating them in vitro with tissue from the patient's tumour. The dendritic cells thereby identify the antigenic make-up of the tumour after which the activated dendritic cells are injected subcutaneously into the patients in aliquots at intervals. Alternatively, in a process still under development, the harvested dendritic cells are injected directly into the tumour where they are activated in situ with the same result. The activated dendritic cells pass information to generations of "killer" T-cells and B-cells so that those immune cells can recognise and attack the tumourous tissue wherever it may be found.
Dendritic cells
Discover in 1973 at Rockefeller University by Dr. Ralph Steinman, dendritic cells act as the general for the adaptive immune system. They educate and direct T-Cells and other immune system cells to mount an immune response to cancer cells. The basic principle behind the therapy is that if one injects or creates a large enough number of dendritic cells carrying mutant proteins matching a cancer, they excite enough T-cells and B-cells to overwhelm the cancer's defenses.[4]
DCVax-L
DCVax-L is a solid-tumor cancer therapy for newly diagnosed GBM, a common and aggressive form of brain cancer. The 5 year survival rate for GBM using current standard of care is 5%. The phase III trial sites include over 80 medical institutions in the U.S., Canada, Germany and the U.K. The results of the trial were peer reviewed and published in the Journal of American Medical Association Oncology in Nov 2022. The trial showed a meaningful increase in survival for both new diagnosed and recurrent GBM patients. For newly diagnosed the median overall survival was 19.3 months vs. 16.5 months in the external control group. The 60 month survival rate was 13% vs. 5.7%. For recurrent GBM the mean overall survival rate was markedly higher at 13.2% vs 7.8%. Over 2,100 doses of DCVax-L were administer with only 5 serious adverse advents.
In this variation of the DCVax line, the tumor is removed through surgery, and some of the tumor presented to the aforementioned dendritic cells for the scavenging of tumor proteins. These dendritic cells, laden with tumor protein antigens, are then injected under the skin near lymph nodes. The dendritic cells then travel to the local lymph node where the dendritic cells present the proteins to the T- and B-cells, as previously described.[5]
These dendritic cells are grown in the lab from stem cells extracted from the patient's blood.[citation needed] Only a sugar-cube-sized sample of the tumor is needed for subsequent presentation to the dendritic cells. The tumor sample is first broken down into constituent proteins using a caustic process known as lysing (thus the L in the name DCVax-L). After the resulting "tumor lysate" is presented to the dendritic cells, they are ready for subcutaneous injection near the selected lymph node(s). (There are approximately 500 lymph nodes in the body; most are peripheral, some are internal.)
DCVax-Direct
DCVax-Direct, the latest addition to the DCVax line. It does not require removal of the tumor, making it ideal for inoperable tumors, if proven effective. It is currently in Phase 1 testing on patients with inoperable tumors of a very large range of cancer types.
In the procedure, dendritic cells are developed as in DCVax-L, prior to antigen exposure/"pulsing". However, the subsequent exposure to tumor antigens does not occur in vitro but in vivo: The prepared dendritic cells, along with adjuncts, are injected directly into one or more tumors.
At least two adjuncts are added to the dendritic cells. One adjunct excites a general aspect of the body's immune response; another excites a more tumor-specific response.[citation needed] This mixture is then injected into the patient's tumor. There, the dendritic cells are expected to scavenge tumor proteins, then find their way to the local lymph node for presentation of the tumor protein antigens to T cells and B cells. The activated T and B cells then travel to the tumor and kill tumor cells. Ruptured tumor cells release more mutant proteins that are picked up by dendritic cells and other immune cells, and are carried to the lymph nodes to excite still more B and T cells. Theoretically, this cycle repeats, accelerates, then levels off at a high but safe level. The Phase 1 trial that finished enrollment in July, 2014 seeks to confirm this.
DCVax-L and DCVax-Direct, if effective, could address virtually all forms of solid tumor cancers, operable and inoperable, with the possible exception of prostate cancer.[why?]
Products
DCVax-L is now in Phase 3 trials in USA & Europe. It was awarded orphan drug status.
DCVax-Direct is a therapy to treat inoperable solid tumors in Phase 1 trials in the US.
DCVax-Prostate finished Phase 2 trials and has been approved for Phase 3 trials in the US.
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include B and T cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles including cancer cells, but have no detoxification function.
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 immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.
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 are "autologous", being prepared from samples taken from the patient, and are specific to that patient.
This is a list of terms related to oncology. The original source for this list was the US National Cancer Institute's public domain Dictionary of Cancer Terms.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.
An antigen-presenting cell (APC) or accessory cell is a cell that displays an antigen bound by major histocompatibility complex (MHC) proteins on its surface; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T cells.
Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation.
Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.
Ipilimumab, sold under the brand name Yervoy, is a monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
Cancer immunology (immuno-oncology) is an interdisciplinary branch of biology and a sub-discipline of immunology that is concerned with understanding the role of the immune system in the progression and development of cancer; the most well known application is cancer immunotherapy, which utilises the immune system as a treatment for cancer. Cancer immunosurveillance and immunoediting are based on protection against development of tumors in animal systems and (ii) identification of targets for immune recognition of human cancer.
Epithelioid sarcoma is a rare soft tissue sarcoma arising from mesenchymal tissue and characterized by epithelioid-like features. It accounts for less than 1% of all soft tissue sarcomas. It was first definitively characterized by F.M. Enzinger in 1970. It commonly presents itself in the distal limbs of young adults as a small, soft mass or a cluster of bumps. A proximal version has also been described, frequently occurring in the upper extremities. Less commonly, cases are reported in the pelvis, vulva, penis, and spine.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy. It was initially regarded as a form of lymphocyte-derived cutaneous lymphoma and alternatively named CD4+CD56+ hematodermic tumor, blastic NK cell lymphoma, and agranular CD4+ NK cell leukemia. Later, however, the disease was determined to be a malignancy of plasmacytoid dendritic cells rather than lymphocytes and therefore termed blastic plasmacytoid dendritic cell neoplasm. In 2016, the World Health Organization designated BPDCN to be in its own separate category within the myeloid class of neoplasms. It is estimated that BPDCN constitutes 0.44% of all hematological malignancies.
Dendreon is a biotechnology company. Its lead product, Provenge, is an immunotherapy for prostate cancer. It consists of a mixture of the patient's own blood cells that have been incubated with the Dendreon PAP-GM-CSF fusion protein. Phase III clinical trial results demonstrating a survival benefit for prostate cancer patients receiving the drug were presented at the AUA meeting on April 28, 2009. After going through the approval process, Provenge was given full approval by the FDA on April 29, 2010. Dendreon's stock value fell 66% on August 4, 2011, after abandoning its forecast for its debut drug Provenge.
Pelareorep is a proprietary isolate of the unmodified human reovirus being developed as a systemically administered immuno-oncological viral agent for the treatment of solid tumors and hematological malignancies. Pelareorep is an oncolytic virus, which means that it preferentially lyses cancer cells. Pelareorep also promotes an inflamed tumor phenotype through innate and adaptive immune responses. Preliminary clinical trials indicate that it may have anti-cancer effects across a variety of cancer types when administered alone and in combination with other cancer therapies.
Gustav Gaudernack is a scientist working in the development of cancer vaccines and cancer immunotherapy. He has developed various strategies in immunological treatment of cancer. He is involved in several ongoing cellular and immuno-gene therapeutic clinical trials and his research group has put major efforts into the development of various T cell-based immunotherapeutic strategies.
ALECSAT technology is a novel method of epigenetic cancer immunotherapy being used by the company CytoVac. It uses a patient's own immune system to target tumor cells in prostate cancer, glioblastomas, and potentially pancreatic cancer. ALECSAT research, directed by Alexei Kirken and Karine Dzhandzhugazyan, has led to several clinical trials.
Tolerogenic therapy aims to induce immune tolerance where there is pathological or undesirable activation of the normal immune response. This can occur, for example, when an allogeneic transplantation patient develops an immune reaction to donor antigens, or when the body responds inappropriately to self antigens implicated in autoimmune diseases. It must provide absence of specific antibodies for exactly that antigenes.
Eftilagimod alpha is a large-molecule cancer drug being developed by the clinical-stage biotechnology company Immutep. Efti is a soluble version of the immune checkpoint molecule LAG-3. It is an APC Activator used to increase an immune response to tumors, and is administered by subcutaneous injection. Efti has three intended clinical settings:
The dendritic cell-based cancer vaccine is an innovation in therapeutic strategy for cancer patients.
Whole-cell vaccines are a type of vaccine that has been prepared in the laboratory from entire cells. Such vaccines simultaneously contain multiple antigens to activate the immune system. They induce antigen-specific T-cell responses.
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