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Immunotherapy

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.

Cancer immunotherapy

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.

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.

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.

Cancer immunotherapy companies
CAR-T cells and TCR engineered cells for cancer treatment

Abbvie - Using Calibr's switchable CAR-T platform against solid tumors and other cancers

Calibr - modular ‘switchable’ CAR-T cell that uses antibody-based switch molecules, working towards universal CAR-T based treatments for hematological and solid cancers

Allogene Therapeutics - Using UCART19 against CD19-expressing hematological malignancies, acute lymphoblastic leukemia

Amgen - Using engineered autologous cell therapy (eACT™) platform from Kite Pharma

Atara Biotherapeutics- Off-the-shelf, allogeneic T-cell immunotherapy

Autolus Limited

Bellicum Pharmaceuticals - GoCAR-T cells incorporates an activation switch needing both the target cancer cells and rimiducid

bluebird bio - Partnered with Celgene, developing a CAR-T therapy called bb2121 targeting b-cell maturation antigen (BCMA) for multiple myeloma

Carina Biotech

CARsgen Therapeutics - anti-Claudin18.2-CAR-T for gastric and pancreatic cancer began a Phase I clinical trial in 2017

Celgene

Cellectis - creating “off-the-shelf” allogeneic products called universal chimeric antigen receptor T-cells (UCART)

Cell Medica

Cell Design Labs - Throttle™, CAR-T cells with small molecule control of an “on/off” switch and synNotch™, a synthetic gene expression system in CAR-T cells for better tumor recognition and specificity

Celularity - CAR constructs for allogeneic CAR-T/NK products

Celyad - CAR-T NK cell-based immunotherapies for cancer

Fate Therapeutics - off-the-shelf CAR T-cell product candidate FT819 derived from iPS Cells

Fortress Bio

Gilead Sciences

Janssen Biotech - Experimental CART-cell therapy LCAR-B38M for myeloma

Juno Therapeutics

JW Therapeutics

Kite Pharma - CAR-T cell therapy called Yescarta U.S. FDA approved for treatment of relapsed or refractory large B-cell lymphoma

Medisix Therapeutics

Mustang Bio - proprietary CAR-T technology and developing CAR-T therapies with CRISPR/Cas9 for hematologic malignancies and solid tumors

Nanjing Legend Biotech

Novartis - U.S. FDA approved CAR-T cell therapy, Kymriah, which uses self-derived cells for treatment of B-cell acute lymphoblastic leukemia

Pfizer - Phase I clinical trials ongoing as of 2018 for allogeneic CAR-T cell therapy UCART19

Precision BioSciences - Collaborating with Baxalta to develop allogeneic CAR-T therapies

Poseida Therapeutics - P-PSMA-101, a PSMA-specific stem cell memory CAR-T drug candidate for prostate cancer

Shire

Sorrento Therapeutics - anti-CEA CAR-T in clinical trials with patients with carcinoembryonic antigen–positive (CEA+) cancers

Zencapsule - develops delivery systems for immune checkpoint inhibitors

Ziopharm - non-viral “Sleeping Beauty” (SB) platform for manufacturing of genetically modified CAR+ T cells

Metabolic immuno-oncology

Agios Pharmaceuticals - Partnered with Celgene for a metabolic immune-oncology approach that involves altering the metabolic state of immune cells to enhance the immune response to cancer

Immune checkpoint inhibitors

PD-1 inhibitors include pembrolizumab and nivolumab.

PD-L1 inhibitors include atezolizumab, avelumab, and durvalumab.

Autoimmune disorder immunotherapy
B cell depletion therapies (BCDTs)

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.

Therapies that target Tregs

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.

Timeline

Further Resources

Title
Author
Link
Type
Date

CAR-T Companies: The Meteoric Rise Of Cellular Immunotherapies

Web

The Future of Immunotherapy: A 20-Year Perspective

Web

News

Title
Author
Date
Publisher
Description
May 18, 2021
BioSpace
Nektar Therapeutics Announces its First Publication of Preclinical Data Highlighting Anti-Tumor Properties of IL-15 Agonist, NKTR-255, in the Journal for ImmunoTherapy of Cancer (JITC) - read this article along with other careers information, tips and advice on BioSpace
Alligator Bioscience
May 5, 2021
www.prnewswire.com:443
/PRNewswire/ -- Alligator Bioscience (Nasdaq Stockholm: ATORX) today announced that preclinical data on its agonist anti-CD40 antibody mitazalimab has been...
Research and Markets
April 30, 2021
www.prnewswire.com:443
/PRNewswire/ -- The "Allergy Treatment Market Forecast to 2028 - COVID-19 Impact and Global Analysis By Allergy Type (Eye Allergy, Rhinitis, Asthma, Skin...
Financialnewsmedia.com
January 25, 2021
www.prnewswire.com:443
/PRNewswire/ -- Ovarian cancer is one of the most deadly gynecologic malignancy across the globe, but new treatments are gaining increased efficacy while...
AACC
December 13, 2020
www.prnewswire.com:443
/PRNewswire/ -- In the wake of the novel coronavirus pandemic, the need for reliable, accurate, and accessible laboratory testing is more evident than ever...
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References

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