Immunotherapy
Immunotherapy aims to treat disease through activation or suppression of an immune response. For example activating immunotherapies can target cancer and suppressive immunotherapies can target autoimmunity.
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Regulatory T cells (Tregs) are a subset of CD4+ T lymphocytes that have immunosuppressive effects, and play an important for in the immune response to self-antigens and have a role in maintaining self-tolerance. Autoimmune diseases develop from a loss of self-tolerance and chronic immune responses against the body’s own cells, tissues and organs. Therapeutic strategies aim to induce or expand Tregs in order to increase the anti-inflammatory and tolerogenic activities of the immune system.
B cell depletion therapies (BCDTs) are used to prevent B cell lymphomas from reoccurring. The treatments are reagents such as anti-CD20, anti-CD19 and anti-BAFF antibodies that bind surface glycoproteins on B cells. BCDTs are also being developed to treat autoimmune diseases in which B cells are involved.
BCDT drugs in clinical trials for treatment of multiple sclerosis include the anti-CD20 and anti-CD19 drugs rituximab and ublituximab. Ocrelizumab and ofatumumab are anti-CD20 treatments approved for relapsing multiple sclerosis. Ocrelizumab, obinutuzumab, obexelimab, obexelimab and rituximab are anti-CD20 and anti-CD19 treatments in clinical trials for treatment of systemic lupus erythematosus.
The BAFF inhibitor, anti-BAFF, belimumab is approved for systemic lupus erythematosus. BAFF is a key survival factor on B cells. Belimumab blocks binding of BAFF to BAFF receptors on B cells. Several anti-BAFF treatments are in clinical trials for autoimmune diseases such as Sjogren syndrome, rheumatoid arthritis and neuromyelitis optica spectrum disorders (NMOSD).
Inhibiting Bruton tyrosine kinase (BTK), expressed in B cells and myeloid cells, is another strategy for removing B cells. Small molecule BTK inhibitors are in clinical trials for multiple sclerosis.
CAR-T cell therapy targeting anti-CD19 is in clinical trial stage for systemic lupus erythematosus. As an alternative to using an anti-CD20 antibody (Rituximab) for B cell depletion, CAR-T cell therapy in which CD8+ T cells express CD19-targeted chimeric antigen receptros (CARs) were used to deplete B cells expressing CD19. CAR-T cell therapy targeting anti-BCMA is in clinical trials for myasthenia gravis and multiple myeloma. Anti-desmoglein 3 is targeted by the CAR-T therapy in clinical trials for mucosal-dominant pemphigus vulgaris.
Zencapsule - develops delivery systems for immune checkpoint inhibitors
PD-1 inhibitors include pembrolizumab and nivolumab.
PD-L1 inhibitors include atezolizumab, avelumab, and durvalumab.
Poseida Therapeutics - P-PSMA-101, a PSMA-specific stem cellstem cell memory CAR-T drug candidate for prostate cancer
Tumors are thought to perpetuate their survival by reprogramming the metabolism of the host. Since increased metabolic stress can decrease antitumor T-cell immune response some cancer immunotherapycancer immunotherapy strategies aim to normalize metabolic stress.
bluebird bio - Partnered with CelgeneCelgene, developing a CAR-T therapy called bb2121 targeting b-cell maturation antigen (BCMA) for multiple myeloma
Poseida Therapeutics - P-PSMA-101, a PSMA-specific stem cell memory CAR-T drug candidate for prostate cancerprostate cancer
Malignant tumors can be detected by natural killer (NK) cells and T-cells of the immune system because they display tumor-specific antigens, also called neoantigens, which result from mutations in the tumor genome, and are recognized as non-self. Tumor-associated antigens (TAAs) are proteins more abundant on the surface of cancer cellscancer cells compared to normal cells and can initiate a T-cell anti-cancer response. TAAs are shared by a subgroup of patients but neoantigens are unique to individual patient tumors. Tumors acquire certain characteristics that help them evade immune detection and the tumor micro-environment creates an immunosuppressive network.
Amgen - Using engineered autologous cell therapy (eACTTM) platform from Kite PharmaKite Pharma
CARsgen Therapeutics - anti-Claudin18.2-CAR-T for gastric and pancreatic cancerpancreatic cancer began a Phase I clinical trial in 2017
Tumors are thought to perpetuate their survival by reprogramming the metabolism of the host. Since increased metabolic stress can decrease antitumor T-cell immune response some cancer immunotherapy strategies aim to normalize metabolic stress.
Tumors are thought to perpetuate their survival by reprogramming the metabolism of the host. Since increased metabolic stress can decrease antitumor T-cell immune response some cancer immunotherapy strategies aim to normalize metabolic stress.
Immune checkpoint proteins are involved in controlling immune responses. Cancers can activate immune checkpoint mechanisms resulting in suppression of the immune system’s anti-tumor response. Immune checkpoint inhibitors are a type of immunotherapy which utilises antibodies to block immune checkpoint proteins.
Malignant tumors can be detected by natural killer (NK) cells and T-cells of the immune system because they display tumor-specific antigens, also called neoantigens, which result from mutations in the tumor genome, and are recognized as non-self. Tumor-associated antigens (TAAs) are proteins more abundant on the surface of cancer cells compared to normal cells and can initiate a T-cell anti-cancer response. TAAs are shared by a subgroup of patients but neoantigens are unique to individual patient tumors. Tumors acquire certain characteristics that help them evade immune detection and the tumor micro-environment creates an immunosuppressive network.
To enhance the ability of T-cells and NK cells to kill cancer cells, immune cells are generated with modified T-cell receptors (TCRs) or expressing chimeric antigen receptors (CARs) designed to target various tumor antigens and neoantigens. Either the patient's own cells (autogeneic) or allogeneic cells are used to generate these types of immunotherapies.
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