Immunotherapy has been widely studied in cancer treatment research, ever since William Coley, who is regarded as the father of immunotherapy, first attempted to leverage the immune system for oncological therapy in 1891.\n\n\n\nSoon enough, the transformative power of cancer vaccines were observed where tumor-specific antigens triggered antitumor immune responses. Along with these technological advancements, cytokine and CAR-T cell therapies stirred the global oncology sector, particularly in the treatment of aggressive leukemias. \n\n\n\nMeanwhile, immunotherapies have long been used to treat allergies, and have been a turning point in autoimmune disorders research, specifically CAR-T cell therapy. One in particular, is a therapy based on CAR-T cell technology, where the T cells are engineered to attack the autoimmune B cells; a therapy which is currently undergoing clinical trials for the treatment of myasthenia gravis - a disorder that causes muscle weakness and breathing difficulties. \n\n\n\nNow, as more biopharmas delve into cancer research, here are ten companies which are shaking the scene in the healthcare industry with their novel approaches in immunotherapy.\n\n\n\n\n\nElevateBio\n\n\n\nSituated in Massachusetts, a global biotech hotspot, ElevateBio is a U.S.-based biotech that specializes in cell and gene therapies, particularly in the prevention of leukemia relapses. Founded in 2017, the company is developing technologies in gene editing, vector engineering and induced pluripotent stem cells (iPSC) -derived immunotherapies for the treatment of cancers.\n\n\n\nIPSCs are skin and blood cells that have been reprogrammed through methods like gene transfer, where somatic cells are cultured and then genetically modified. A game changer in immunotherapy research, iPSCs are a clinically applicable method for the treatment of diabetes, cancer and even neurodegenerative diseases like Parkinson’s. ElevateBio is looking to develop iPSC-derived therapies, for which it set up a new company in 2022, in a collaborative effort with Boston Children’s Hospital, where it will generate mature immune cells from iPSCs.\n\n\n\nMoreover, the immunotherapy company has partnered with the California Institute for Regenerative Medicine to expedite research in regenerative medicine to develop iPS cell lines suitable for clinical development and commercialization. \n\n\n\nOver the years, ElevateBio has raised more than $845 million in funding, with its most recent investors being for-profit charity Emerson Collective and global investor EDBI, for advancement in immunotherapy research.\n\n\n\nPionyr Immunotherapeutics\n\n\n\nAs a clinical-stage company, San Francisco-based Pionyr Immunotherapeutics has various therapies being researched as part of its pipeline. The company, which was set up in 2015, aims to enhance antitumor immunity by targeting tumors through cancer immunotherapies.\n\n\n\nAt the forefront of its pipeline is PY314 for the treatment of advanced solid tumors. The drug is a monoclonal antibody, which is a type of protein that can bind to antigens of cancer cells; flagging the cells and could trigger the destruction of its cell membranes. PY314 targets TREM2 which is found on tumor myeloid cells in order to activate anti-tumor immunity. Pionyr Immunotherapeutics’ drug, which will be used to treat carcinomas and breast cancer, is in its first phase of clinical trials where it is being tested on patients with metastatic solid tumors that are refractory - cancers that do not respond to treatment, and relapsed - cancers that recur after treatment. \n\n\n\nPionyr Immunotherapeutics partnered with the U.S.-based biopharma Gilead Sciences, where the latter invested $275 million in 2020, as Pionyr was granted investigational new drug (IND) status from the U.S Food and Drug Administration (FDA) for two of its drug candidates, including PY314, which allowed the therapies to be tested on patients.\n\n\n\nCARsgen Therapeutics\n\n\n\nBased in the business capital of Shanghai, CARSgen Therapeutics is a China-based biopharma focused on the development of CAR-T cell therapies for the treatment of hematological malignancies and solid tumors. Founded less than a decade ago in 2014, the company’s expansive pipeline has more than ten therapies that are in various phases of development. \n\n\n\nOne of its candidates is CT053, which has been assigned Regenerative Medicine Advanced Therapy (RMAT) designation as well as Orphan Drug status from the FDA. CT053, which is an investigational CAR-T cell therapy, is an anti-B Cell Maturation Antigen (BCMA) autologous chimeric antigen receptor, pivotal in regulating B-cell proliferation. A response rate of 94% in 18 patients was observed as a result of successful clinical trials. One benefit to this therapy is the reduced manufacturing time in comparison with the average CAR T-cell production, where it takes 8 to 10 days between apheresis - the procedure in which blood is collected, platelets and white blood cells are drawn out, and the rest of the blood is returned to the donor - and infusion.\n\n\n\nIn 2023, the company announced its collaboration with Chinese pharma Huadong Medicine for the commercialization of CT053 in mainland China.\n\n\n\nHaving raised around $276 million in funding, the immunotherapy company has also partnered with other organizations like the research center Shanghai Cancer Institute for further research in CAR-T cell therapy for solid tumors.\n\n\n\nAffimed Therapeutics\n\n\n\nYet another biotech that specializes in oncology, Affimed Therapeutics is a German company based in Heidelberg, which has developed a novel technology called ICE. What stands for innate cell engager, ICE is derived from the company’s redirected optimized cell killing (ROCK) platform.\n\n\n\nThe mechanism of ICE is to bind with both innate immune cells and tumor cells, in turn activating the innate immune cells (natural killer cells and macrophages) to kill the tumor cells. Unlike other antibody-based therapies, ICE’s advantage is that it doesn’t compete with the body’s antibodies as its binding with the innate immune cells is said to occur efficiently.\n\n\n\nFounded more than two decades ago, the immunotherapy company recently announced that it was authorized to conduct clinical trials in France for its potential drug candidate AFM28 for the treatment of relapsed and refractory acute myeloid leukemia.\n\n\n\nNodThera\n\n\n\nBesides cancer treatment, immunotherapy can also combat certain inflammatory diseases. UK-based biotech NodThera has built a pipeline that focuses on exactly that. Founded in 2016, the company recently announced positive phase one results for the drug candidates NT-0796 and NT-0249, for the treatment of neuroinflammatory and peripheral inflammatory diseases.\n\n\n\nNT-0796 is an orally available inhibitor of NLRP3, which plays a crucial role in regulating the innate immune system and inflammatory signaling, and causes a pro-inflammatory response. When NT-0796 inhibits NLRP3, it induces an anti-inflammatory effect, without causing drug-related liver function test (LFT) abnormalities.\n\n\n\nNT-0249 is another NLRP3 inhibitor which battles an inflammatory response, and has proven to be efficacious demonstrating pharmacokinetics - the response of the body’s interaction with administered drugs for the entire duration of exposure, which was consistent with a once-a-day therapy.\n\n\n\nAs of 2020, NodThera has raised around $95 million in funding with aid from investment companies like Novo Ventures and venture capital firm 5AM Ventures.\n\n\n\nOrum Therapeutics\n\n\n\nEstablished in the South Korean metropolis Daejeon, Orum Therapeutics focuses on a protein degrader approach, particularly in the ubiquitin-proteasome system, which is notably a potential therapeutic target according to research conducted for Alzheimer’s disease treatment. However, Orum is looking to develop its technology for oncological therapies.\n\n\n\nIn December 2022, the immunotherapy company announced the successful completion of preclinical studies for ORM-615, an anti-CD33 antibody-enabled GSPT1 degrader for acute myeloid leukemia (AML). CD33 is an inhibitory receptor which is expressed on myeloid cells. Excess CD33 in cancer cells can cause the rapid growth of the cells, which ORM-615 aims to tackle. As protein degraders disassemble unwanted proteins, ORM-615 uses an antibody that targets the protein CD33.\n\n\n\nFounded in 2016, the company has various other therapies in its pipeline including treatments for breast cancer and small cell lung cancer (SCLC). Over the years, it has received approximately $92 million in funding with a good portion of its investors being venture capitalists and investment firms.\n\n\n\nArcellx\n\n\n\nKnown for its abundance of blue crabs, Maryland, in the U.S. is home to clinical-stage biopharma Arcellx, which specializes in cell therapies powered by its novel D-Domain technology, among other platforms. Established in 2015, the company intends to improve the safety of CAR-T therapy, which can induce side effects like neurotoxicity and even cytokine release syndrome - an acute inflammatory response which can lead to organ dysfunction.\n\n\n\nThe D-Domain technology uses a binding agent which can enable high cell surface expression and improve target specificity, serving as a foundation for its other platforms in therapeutic research. Arcellx’s drug candidate CART-ddBCMA, which is currently in phase two of clinical studies, received positive phase one results, wherein patients with relapsed and refractory multiple myeloma showed durable responses with toxicities which were manageable and resolved. Prior to this, the drug had obtained Fast Track and Orphan Drug designations from the FDA. \n\n\n\nTwo months ago, the immunotherapy company announced that it had closed a deal with U.S-based biotech Kite, to co-develop and commercialize CART-DdBCMA. Having raised $422 million in funding, the company will further develop its investigational drugs for acute myeloid leukemia and solid tumors.\n\n\n\nTurnstone Biologics\n\n\n\nHeadquartered in Canada’s capital Ottawa, Turnstone Biologics was founded in 2015 to deliver cancer immunotherapies targeting tumor immunity. Its approach is the development of a tumor-infiltrating lymphocyte (TIL) therapy based on potent tumor-reactive T cells. TILs are cultured after its extraction from patients, followed by the infusion of TILs which bolsters an immune response. The therapy works in tandem with chemotherapy, which kills fast-growing cancer cells. \n\n\n\nFor the treatment of certain melanomas, breast cancer and colorectal cancer, the company has collaborated with Moffitt Cancer Center and National Cancer Institute to develop TIDAL-01, a therapy in phase one of its clinical trials. Having obtained clearance as an investigational new drug (IND) from the FDA, the immunotherapy is evolved from TIL technology, and uses a patient’s own immune cells to fight cancer. \n\n\n\nTurnstone Biologics has raised more than $132 million in funding with $80 million in their latest round which took place in 2021, a major investor being healthcare investment advisor PFM Health Sciences.\n\n\n\nInotrem\n\n\n\nSeptic shock is a life-threatening condition that is caused by a drop in the blood pressure following an infection. Left untreated, it can lead to damaged blood vessels, causing the heart’s inability to pump blood to other organs. The most common treatments for septic shock are antibiotics, oxygen therapy and inotropic medicines that stimulate the heart. Moreover, immunotherapy could accelerate expansion in treatment options. \n\n\n\nParis-based biopharma Inotrem strives to accelerate research in immunotherapy for the condition. Studying the biology of TREM-1, an immunoreceptor expressed on innate immune cells, TREM-1 modulates inflammation. Inotrem’s pipeline is based on the TREM-1 pathway with its candidate Nangibotide - a synthetic peptide that blocks TREM-1-mediated immune dysregulations and balances the inflammatory response - in phase two of clinical trials. \n\n\n\nFounded a decade ago, the biotech is also developing therapies for other inflammatory syndromes like inflammatory bowel disease, for which it has received funding from non-profit Crohn’s & Colitis Foundation. As of January 2023, the company has raised €121 million ($129.7 million) in funding.\n\n\n\nHummingbird Bioscience\n\n\n\nBased in the emerging biotech hub of Singapore, Hummingbird Bioscience researches the potential of precision medicine for multiple solid tumors. Founded in 2014, it has raised $150 million in funding, with one of its lead investors Novo Holdings financing $125 million in 2021.\n\n\n\nIn its pipeline is HMBD-001, a candidate that began its first phase in clinical trials in 2021, for cancers like bladder cancer, triple negative breast cancer and prostate cancer, where the cancer had spread to surrounding tissue and even to other parts of the body. It is a monoclonal antibody which targets HER3 cancer cells by blocking the signals for cell proliferation.\n\n\n\nRecently, the company decided to license the trials for HMBD-001 to fast track the next stage in phase one, having joined forces with Cancer Research UK for accelerating the development of its pipeline.\n\n\n\nThese ten companies across the world have made their mark in the biotech industry with novel approaches in immunotherapy. However, the list is not limited to the aforementioned companies as various biotechs have made interesting discoveries and breakthroughs in therapies in the past year.