A TNFi biologic would not be a good choice for those with congestive heart failure, previous serious or recurrent infections or demyelinating disease; and; For patients who have active PsA and concomitant IBD despite treatment with an OSM: Switch to a monoclonal antibody TNFi biologic over a TNFi biologic soluble receptor biologic, which is ineffective for IBD; Switch to a TNFi monoclonal antibody biologic over an IL-17i biologic, which is ineffective for IBD; and; Switch to an IL-12/23i. Monoclonal Antibodies Approved by the EMA and FDA for Therapeutic Use (status 2017) Further information on biopharmaceutical products present in the US and European markets can be found at: www.biopharma.com.
On This Page.What is biological therapy?Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer stimulate the body’s immune system to act against cancer.
These types of biological therapy, which are sometimes referred to collectively as “immunotherapy,” do not target cancer cells directly. Other biological therapies, such as, do target cancer cells directly. Biological therapies that interfere with specific involved in growth and progression are also referred to as. (For more information, see.)For patients with cancer, biological therapies may be used to treat the cancer itself or the of other cancer treatments. Although many forms of biological therapy have been approved by the U.S. Food and Drug Administration (FDA), others remain experimental and are available to cancer patients principally through participation in clinical trials (research studies involving people).What is the immune system?The is a complex network of, and the substances they make.
It helps the body fight infections and other diseases., or, play the main role in. These cells carry out the many tasks required to protect the body against disease-causing microbes and abnormal cells. Some types of leukocytes patrol the circulatory system, seeking foreign invaders, such as microbes and pathogens, and diseased, damaged, or dead cells.
These white blood cells provide a general—or nonspecific—type of immune protection. Other types of leukocytes, known as, provide targeted protection against specific threats, whether from a specific microbe or a diseased or abnormal cell.
The most important groups of lymphocytes responsible for these specific immune responses are and. B cells make, which are large, secreted proteins that bind to and help destroy foreign invaders or abnormal cells., which are also known as cytotoxic T cells, kill infected or abnormal cells by releasing toxic chemicals or by prompting the cells to self-destruct (in a process known as ). Other types of lymphocytes and leukocytes play supporting roles to ensure that B cells and killer T cells do their jobs effectively.
These supporting cells include and, which help activate both B cells and killer T cells and enable them to respond to specific threats from a microbe or a diseased or abnormal cell.are substances on the body’s own cells and on microbes that can be recognized by the immune system. Normal cells in the body have antigens that identify them as “self.” Self antigens tell the immune system that normal cells are not a threat and should be ignored.
In contrast, microbes are recognized by the immune system as a potential threat that should be destroyed because they carry foreign, or non-self, antigens. Cancer cells also often contain antigens, called tumor antigens, that are not present (or are present at lower levels) on normal cells.Can the immune system attack cancer?The natural ability of the to detect and destroy abnormal cells likely prevents or suppresses the development of many cancers. Are sometimes found in and around tumors. These cells, called or TILs, are an indication that the immune system is responding to the tumor. The presence of TILs in a patient’s tumor is often associated with a better in the patient.However, cancer cells have various ways to evade detection and destruction by the immune system.
For example, cancer cells can:. Undergo changes that cause them to reduce the expression of tumor on their surface, making them less “visible” to the immune system.
Have proteins on their surface that inactivate immune cells. Induce normal cells around the tumor (i.e, in the ) to release substances that suppress immune responses and that promote tumor and survival.uses various approaches to strengthen the immune system and/or help it surmount the cancer’s defenses against the immune system. The goal is to improve the ability of the immune system to detect and destroy cancer.What types of biological therapy are used to treat cancer?Several types of biological therapies, especially, are being used or developed for cancer treatment. These therapies fight cancer in different ways.
Immune Checkpoint InhibitorsHow they work: This type of immunotherapy releases a “brake” on the that normally prevents overly strong that might damage normal cells as well as abnormal cells. This brake involves proteins on the surface of called immune checkpoint proteins. When immune checkpoint proteins recognize specific partner proteins on other cells, an “off” signal is sent that tells the T cell not to mount an immune response against those cells.Two widely studied immune checkpoint proteins are. Some tumor cells express high levels of the PD-1 partner protein PD-L1, which causes T cells to shut down and helps the cancer cells evade immune destruction. Similarly, interactions between B7 proteins on and CTLA-4 that is expressed on T cells prevents T cells from killing other cells, including cancer cells.Drugs called (or immune checkpoint modulators) prevent the interaction between immune checkpoint proteins and their partner proteins, enabling a strong immune response. The targets of current checkpoint inhibitors include PD-1, PD-L1, and CTLA-4.How they are used: Immune checkpoint inhibitors are approved to treat a variety of cancer types, including, (a type of kidney cancer),.
One immune checkpoint inhibitor, (Keytruda®), is used to treat any solid tumor that is -high or mismatch repair deficient and has spread or cannot be removed by surgery. Another immune checkpoint inhibitor, (Opdivo®), is used to treat mismatch repair deficient and microsatellite instability-high that has progressed following treatment with a, and.Immune Cell Therapy (also called Adoptive Cell Therapy or Adoptive Immunotherapy)How it works: This approach makes a patient’s own better able to attack tumors. There are two general approaches to for cancer treatment.
Both involve collecting a patient’s own immune cells, growing large numbers of these cells in the laboratory, and then infusing the cells back into the patient. Tumor-infiltrating lymphocytes (or TILs). This approach uses T cells that are naturally found in a patient’s tumor, called (TILs). TILs that best recognize the patient's tumor cells in laboratory tests are selected, and these cells are grown to large numbers in the laboratory.
The cells are then activated by treatment with immune system signaling proteins called and infused into the patient’s bloodstream.The idea behind this approach is that the TILs have already shown the ability to target tumor cells, but there may not be enough of them in the to kill the tumor or to overcome the immune suppressive signals that the tumor is releasing. Introducing massive amounts of activated TILs can help to overcome these barriers.
This approach is similar, but the patient’s T cells are in the laboratory to express a protein known as a, or CAR, before they are grown and infused into the patient. CARs are modified forms of a protein called a, which is expressed on the surface of T cells.
The CARs are designed to allow the T cells to attach to specific proteins on the surface of the patient’s cancer cells, improving their ability to attack the cancer cells.Before receiving the expanded T cells, patients also undergo a procedure called lymphodepletion, which consists of a round of chemotherapy and, in some cases, whole-body radiation. The lymphodepletion gets rid of other immune cells that can impede the effectiveness of the incoming T cells.How it is used: Adoptive T-cell transfer was first studied for the treatment of metastatic melanoma because melanomas often cause a substantial immune response, with many TILs.
The use of activated TILs has been effective for some patients with melanoma and has produced encouraging positive findings in other cancers (e.g., and ).Two CAR T-cell therapies have been approved. (Kymriah™) is approved for treatment of some adults and children with acute lymphoblastic leukemia that is not responding to other treatments and for treatment of adults with certain types of B-cell who have not responded to or who have relapsed after at least two other kinds of treatment. In, many patients’ cancers have disappeared entirely, and several of these patients have remained cancer free for extended periods. (Yescarta™) is approved for patients with certain types of B-cell who have not responded to or who have relapsed after at least two other kinds of treatment. Both therapies involve the modification of a patient’s own immune cells.Therapeutic AntibodiesHow they work: Therapeutic antibodies are antibodies made in the laboratory that are designed to destroy cancer cells.
They are a type of targeted cancer therapy—drugs that are designed specifically to interact with and block a specific molecule (or “molecular target”) that is necessary for cancer cell growth. More information about is available in NCI’s Targeted Cancer Therapies fact sheet.Therapeutic antibodies work in many different ways:.
They may both interfere with a key signaling process that promotes the growth of the cancer and alert the immune system to destroy cancer cells to which the antibody is attached. (Herceptin), which binds to a protein on some cancer cells called, is an example.
Their binding to the target protein may directly cause cancer cells to undergo. Examples of this type of therapeutic antibody are (Rituxan®) and (Arzerra®), both of which target a protein on the surface of called. Similarly, (Campath®), binds a protein on the surface of mature lymphocytes called CD52. They may be linked to a toxic substance that kills cancer cells to which the antibody binds.
The toxic substance can be a poison, such as a; a; a light-sensitive chemical (used in photoimmunotherapy); or a compound (used in ). Antibodies of this type are sometimes called (ADCs). Examples of ADCs used for cancer include (Kadcyla®), which is taken up by and kills cancer cells that express HER2 on their surface, and (Adcetris®), which is taken up by and kills lymphoma cells that express CD30 on their surface.
They may bring activated T cells into close proximity to cancer cells. For example, the therapeutic antibody (Blincyto®) binds to both CD19, a tumor-associated antigen that is overexpressed on the surface of leukemia cells, and CD3, a on the surface of T cells that is part of the T-cell receptor. Blinatumomab brings leukemia cells into contact with T cells, resulting in T-cell activation and a killer T-cell response against CD19-expressing leukemia cells.Other immunotherapies combine other (non-antibody) immune system molecules and cancer-killing agents. For example, (ONTAK®) consists of the cytokine (IL-2) attached to a toxin produced by the bacterium Corynebacterium diphtheria, which causes diphtheria. Denileukin diftitox uses its IL-2 portion to target cancer cells that have IL-2 receptors on their surface, allowing the diphtheria toxin to kill them.How they are used: Many therapeutic antibodies have been approved to treat a wide variety of cancers.Therapeutic VaccinesHow they work: Cancer treatment vaccines are designed to treat cancers that have already developed by strengthening the body’s natural defenses against the cancer. Selected References.Sutlu T, Alici E. Natural killer cell-based immunotherapy in cancer: current insights and future prospects.
Journal of Internal Medicine 2009; 266(2):154-181.Joshi S, Kaur S, Redig AJ, et al. Type I interferon (IFN)-dependent activation of Mnk1 and its role in the generation of growth inhibitory responses. Proceedings of the National Academy of Sciences U S A 2009; 106(29):2.Jonasch E, Haluska FG. Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities.
The Oncologist 2001; 6(1):34-55.Li Y, Liu S, Margolin K, et al. Summary of the primer on tumor immunology and the biological therapy of cancer. Journal of Translational Medicine 2009; 7:11.Grimaldi AM, Marincola FM, Ascierto PA. Single versus combination immunotherapy drug treatment in melanoma.
Expert Opinion on Biological Therapy 2016; 16(4):433-441.Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy.
Cell 2017; 168(4):707-723.Wu X, Giobbie-Hurder A, Liao X, et al. Angiopoietin-2 as a biomarker and target for immune checkpoint therapy.
Cancer Immunology Research 2017; 5(1):17-28.Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. DNA damage and repair biomarkers of immunotherapy response.
Cancer Discovery 2017; 7(7): 675-693.Duan F, Duitama J, Al Seesi S, et al. Genomic and bioinformatic profiling of mutational neoepitopes reveals new rules to predict anticancer immunogenicity. Journal of Experimental Medicine 2014; 211(11):2231-2248.Kreiter S, Vormehr M, van de Roemer N, et al. Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 2015; 520(7549):692-696.Gros A, Parkhurst MR, Tran E, et al. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients.
Nature Medicine 2016; 22(4):433-438.Nagaya T, Nakamura Y, Sato K, et al. Near infrared photoimmunotherapy with an anti-mesothelin antibody. Oncotarget 2016; 7(17):9.Ogawa M, Tomita Y, Nakamura Y, et al. Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity. Oncotarget 2017; 8(6):6.Railkar R, Krane LS, Li QQ, et al. Epidermal growth factor receptor (EGFR)-targeted photoimmunotherapy (PIT) for the treatment of EGFR-expressing bladder cancer.
Molecular Cancer Therapeutics 2017; 16(10):2201-2214.
.Monoclonal Antibody Production ServiceMonoclonal antibody can be produced via traditional hybridoma technology or technology. As an internationally recognized antibody expert, Biologics International Corp (BIC) provides monoclonal antibody production services which cover the complete full range of the antibody production process from antigen design through antibody purification.
Our dedicated teams strive to work with each customer to successfully develop high performance monoclonal antibodies. BIC ensures that the ELISA titer of the monoclonal antibodies is greater than 1: 128,000. No other company in the world can gurantee the same titer.Service Highlights.
No mAb delivery no payment. Guaranteed ELISA titer (1:128,000). Positive western blot results. Two positive clones. In-house antigen design tools.
Soluble antigen production and optimization: maximal native epitopes. Strict confidentiality: no project-associated information and clones will be disclosed except to the ownerService ContentsOur monoclonal antibody production service is divided into five phases, enabling each part of the service to be customized. For any question regarding our available packages and how to select these, please and we will be happy to help you. PhaseStandard PackageCustomizableAntigen preparation(optional)BIC offers services for peptide synthesis and protein antigen expression for use as the immunogen. Further, we offer antigen design assistance with no additional charge.Alternatively, customers can provide their own high purity proteins (90%) for use as the immunogen.Phase IImmunization(8 weeks)Five balb/c mice are immunized with multiple rounds of immunogens and test-bled (ELISA test is employed) over a two months period.
Serum and ELISA results are then sent to the customer for evaluation.The number or species of immunized animals is available on request, like two New Zealand white rabbits.Phase IICell fusion(3 weeks)Two mice with the best ELISA titer are chosen, and their spleen cells are harvested for hybridoma fusion. Supernatant from the hybridoma clones will be screened using ELISA, 1 to 2 mL of which is sent to the customer for evaluation.The number of hybridoma cells or the volume of the supernatant can be customized as per customer requirements.Phase IIISubcloning(5 weeks)Parental cell lines can be subcloned through limiting dilution to obtain monoclonal cell lines with clonality and long-term stability. This process includes two rounds of limiting-dilution subcloning and screening.Additional rounds of subcloning can be added at the customer’s request.Phase IVProduction & purification(3 weeks)Target monoclonal antibodies are produced in cell culture in roller bottles.
The antibodies in supernatants are purified via affinity purification using Protein A or Protein G resin.Phase VQC(1 week)In the standard package, BIC offers 2-5 positive cell lines, 2-5 mg purified antibody and 100 μg soluble antigen. We guarantee a positive western blot and an ELISA titer of 1:128,000.We can also offer small scale (up to 500 mg) and large scale (starting from 10 g upwards) antibody production according to customer’s specific needs.The Process of Monoclonal Antibody ProductionAfter having performed thousands of projects, we have the capacity of producing antibodies in either research quantities or in large scale production, and provide comprehensive service packages for monoclonal antibody development. For project quotations and more detailed information. Learn more about.Based on our customized solutions and extensive experience, we provide the following two optional services: Optional Services.