Burkitt Lymphoma

Researchers have shown that targeting a gene regulated by two cancer-fuelling proteins can kill cancerous cells and halt their growth in laboratory models of B-cell acute lymphoblastic leukemia (ALL). Researchers have found a new way to potentially treat one of the most common forms of acute lymphoblastic leukaemia. The study, led by WEHI and the Peter MacCallum Cancer Centre, was able to kill leukaemia cells in the lab and stop cancer cells from growing, after identifying two new proteins critical for the development of the aggressive disease. The findings could lead to enhanced treatment options in the future, with plans underway to develop a clinical trial based on the research. Around 5200 people are diagnosed with a form of leukaemia in Australia each year. An estimated 1500 of these cases are acute -- meaning the blood cancer appears suddenly and grows quickly. Blood cancers like leukaemia are notoriously difficult to treat in adults, with 50% of Australian patients relapsing after the first round of chemotherapy and subsequently becoming resistant to further treatments. Associate Professor Ashley Ng, a corresponding author on the paper, said this presented a unique treatment challenge for these blood cancers and highlighted the urgent need for new therapeutics. "About 135,000 people live with a blood cancer or blood disorder in Australia, with 16 people dying every day from the disease," Assoc Prof Ng, a WEHI researcher and clinical haematologist at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, said. "Despite the medical advancements made in the cancer field over the years, the incidence of blood cancer has grown by 47% in the past decade. "The best way to enhance treatment options for patients is to continually improve our understanding of how leukaemia cancers behave and what drives their growth. "Our new research has identified two proteins that are critical for the development of B-cell acute lymphoblastic leukaemia, expanding our knowledge into how these cancers can form. "By uncovering this new vulnerability in leukaemia formation, we hope to exploit the findings for therapeutic benefit and also apply them to other forms of the disease." The research is published in the journal Science Advances. Master regulators Assoc Prof Ng has spent over a decade researching a protein that regulates gene activity in the cell nucleus, known as ERG. Imbalances in this protein can lead to blood cancers, like acute lymphoblastic leukaemia. His previous research uncovered the protein's critical role in Down syndrome associated blood disease and normal blood cell function, including how B cells -- which are essential for producing antibodies to fight against infections -- develop. First author Dr Kira Behrens said the research team wanted to understand what other types of proteins ERG works with to fuel leukaemia development. "We looked at the proteins that control how specific genes switch 'on' or 'off' to analyse how normal B-cells -- and critically -- B-cell acute lymphoblastic leukaemia -- can develop," Dr Behrens said. "After analysing the genes regulated by ERG and another protein, c-MYC, we discovered that these proteins were actually the master regulators of several important pathways and processes within the leukaemia cell." Researchers then narrowed the list down to focus on one pathway essential for making proteins, known as ribosome biogenesis. This led the team to focus on targeting a key gene essential to this pathway, POL I, which is also controlled by these master regulator proteins. The gene helps direct an important cell growth and division process that can lead to the development of cancer if it goes awry. Dr Behrens said: "By targeting POL I with inhibitors, we were able to kill leukaemia cells and stop their growth in our pre-clinical and human tissue models." "This was a surprising, yet remarkable discovery, as we were able to unravel a new pathway and potential drug target that can hopefully be used in the fight against leukaemia in the future." The study also involved a collaboration with Associate Professor Elaine Sanij (St. Vincent's Institute of Medical Research) whose work focuses on targeting POL I and ribosome biogenesis in cancer therapy. "The findings show that a subset of aggressive acute lymphoblastic leukaemia exhibit a form of addiction to producing of ribosomes, the protein making molecular machinery," Assoc Prof Sanij said. "They render this aggressive leukaemia sensitive to POL I inhibitors which target ribosome production. "Altogether, our work highlights the importance of developing this new approach to cancer therapy to treat oncogene-driven cancers." Collaborative power One of the drugs used in the study to target POL I was an agent developed by the Peter MacCallum Cancer Centre. Professor Rick Pearson, former Associate Director of Laboratory Research at Peter Mac, said the team hopes to mimic the study in a future clinical trial to help patients with acute lymphoblastic leukaemia. "We worked with WEHI researchers to confirm our agent is effective in targeting POL I activity and demonstrated its potency in impeding the leukaemia cell growth and division. "These findings highlight the power of collaboration and the remarkable results that can be achieved when bringing together experts from across various areas. "We hope this research will translate into successful clinical trials and potentially offer doctors a new treatment option for patients with acute lymphoblastic leukaemia," Professor Pearson said. This research was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft), the National Health and Medical Research Council (NHMRC), Cancer Council Victoria, National Stem Cell Foundation of Australia, the Leukaemia Foundation and Victorian Cancer Agency. The study, "ERG and c-MYC Regulate a Critical Gene Network in BCR::ABL1-Driven B-cell Acute Lymphoblastic Leukaemia," is published in Science Advances.

Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. Studies of interactions between two lab-generated monoclonal antibodies (mAbs) and an essential Epstein-Barr virus (EBV) protein have uncovered targets that could be exploited in designing treatments and vaccines for this extremely common virus. The research was led by Jeffrey I. Cohen, M.D., and colleagues from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Study findings were published in the journal Immunity. Approximately 95% of the world's population is infected with EBV, which remains in the body permanently, typically in B lymphocytes, which are antibody-producing immune system cells, and cells lining the throat and pharynx. EBV can sometimes lead to B-cell cancers, including Burkitt, Hodgkin and non-Hodgkin lymphomas, or to gastric or nasopharyngeal cancers. Recently, EBV infection was shown to significantly raise the risk of developing multiple sclerosis. There is no vaccine to prevent EBV infection nor a specific treatment. In this study, NIAID investigators examined a viral protein called gp42, which the virus must use to infect B cells. Theoretically, a vaccine or antibody-based treatment capable of blocking gp42's ability to bind to or fuse with B cells would prevent EBV infection and, thus, the virus's ability to persist in those cells. The team generated two gp42-specific mAbs, A10 and 4C12, and used X-ray crystallography to visualize how they interacted with gp42. The crystal structures revealed that the two mAbs interacted with distinct, non-overlapping sites on gp42. Monoclonal antibody A10 blocked the site on gp42 required for receptor binding, while 4C12 interfered with a different site that is involved in membrane fusion. Next, the scientists tested A10, 4C12 and several other mAbs in mice for their ability to prevent EBV infection and EBV lymphomas. The mAb A10 provided nearly complete protection against EBV infection and none of the mice developed lymphoproliferative disease or lymphoma. In contrast, nearly all the mice treated with other mAbs became infected and some developed lymphoproliferative disease or lymphoma. If future studies show mAb A10 to be safe and effective in humans, it could have clinical applications, particularly in people who have not been infected with EBV; those with immunodeficiency conditions, including severe combined immunodeficiency; or people receiving transplants. People with such conditions are at risk of developing severe or fatal cases of EBV disease during their initial encounter with the virus. The investigational monoclonal antibody could potentially be used prophylactically to prevent or better control EBV infections in such cases, the investigators note. Additionally, the study team suggests that identification of the vulnerable sites on gp42 also paves the way to designing future vaccines that could elicit antibodies against one or both of the newly described sites.

Phase 1/2 study is evaluating IPH6501, a first-in-class CD20-targeting tetraspecific natural killer cell engager, from ANKET® platform, for the treatment of CD20-expressing B-cell Non-Hodgkin's Lymphomas. MARSEILLE, France--(BUSINESS WIRE)-- Regulatory News: Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”) today announced the first patient was dosed in its Phase 1/2 multicenter trial (NCT06088654), investigating the safety and tolerability of IPH6501 in patients with Relapsed and/or Refractory CD20-expressing B-cell Non-Hodgkin’s Lymphoma (NHL). IPH6501 is Innate’s first-in-class CD20-targeting tetraspecific ANKET® (Antibody-based NK cell Engager Therapeutics) that co-engages CD20 as a target antigen on malignant B cells and three receptors on NK cells: two activating receptors (NKp46 and CD16) and the interleukin-2 receptor (but not its alpha subunit), with a human IL‑2 variant, hence providing proliferation and activation signals targeted to NK cells and promoting their cytotoxic activity against CD20 expressing malignant cells. The study is planned to enroll up to 184 patients. “We are pleased to announce the dosing of a first patient in this Phase 1/2 study evaluating IPH6501, our proprietary ANKET® asset and the first tetraspecific NK Cell Engager to enter the clinic.” commented Dr Sonia Quaratino, Chief Medical Officer at Innate Pharma. “With the addition of the IL-2 variant, our second generation ANKET® molecules can deliver proliferation signals to NK cells, and thus enhance their effector functions against cancer cells. Thanks to this novel format, IPH6501 represents a promising alternative strategy to T cell therapies for patients with B-cell non-Hodgkin’s lymphomas.” “The discovery and implementation of novel chemotherapies, T-cell based immunotherapies and targeted therapies have improved outcomes for patients with B-cell non-Hodgkin’s lymphomas compared with traditional chemotherapy.” added Dr Lorenzo Falchi, Lymphoma Specialist at the Memorial Sloan Kettering Cancer Center, New-York, and principal investigator of the study. “However, many patients fail to achieve a response to or develop disease relapse after treatment. In this context, IPH6501 represents an innovative option for the treatment of patients with R/R B-cell non-Hodgkin’s lymphomas and has the potential to fulfil a large unmet need.” More information about the trial can be found on clinicaltrials.gov. About B-Cell Non-Hodgkin’s Lymphoma B-cell lymphomas are clonal tumors of mature and immature B cells that constitute the majority (80-85%) of NHLs. NHLs are a heterogeneous group of lymphoproliferative malignancies. NHL usually originates in the lymphoid tissues and can spread to other organs. NHL is the most common hematological malignancy worldwide, accounting for nearly 3% of cancer diagnoses and deaths. According to the latest World Health Organization (WHO) classification, the most common B-NHL in Western countries is Diffuse large B cell lymphoma (DLBCL), accounting for around 31% of adult cases. Other common aggressive B-cell subtypes include Mantle Cell Lymphoma (MCL) (6% of cases) and Burkitt lymphoma (BL) (2% of cases). Among indolent B-cell NHL, Follicular Lymphoma (FL) accounts for 22% of cases in the Western world, followed by marginal zone lymphoma (MZL) (8% of cases). About IPH6501 IPH6501 is the first Antibody-based NK cell Engager Therapeutic to co-engage activating receptors on NK cells (NKp46 and CD16), IL-2R (but not α subunit) through a variant of human IL-2, and a tumor antigen (CD20) via a single molecule, hence providing proliferation and activation signals targeted to NK cells and promoting their cytotoxic activity against CD20 expressing malignant cells. IPH6501 has shown better anti-tumor efficacy than approved benchmark antibodies in preclinical tumor models (Demaria, EHA 2023). About ANKET® ANKET® (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multispecific natural killer (NK) cell engagers to treat certain types of cancer. This fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer. About Innate Pharma Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for cancer patients. Its innovative approach aims to harness the innate immune system through therapeutic antibodies and its ANKET® proprietary platform. Innate’s portfolio includes lead proprietary program lacutamab, developed in advanced form of cutaneous T cell lymphomas and peripheral T cell lymphomas, monalizumab developed with AstraZeneca in non-small cell lung cancer, as well as ANKET® multi-specific NK cell engagers to address multiple tumor types. Innate Pharma is a trusted partner to biopharmaceutical companies such as Sanofi and AstraZeneca, as well as leading research institutions, to accelerate innovation, research and development for the benefit of patients. Headquartered in Marseille, France with a US office in Rockville, MD, Innate Pharma is listed on Euronext Paris and Nasdaq in the US. Learn more about Innate Pharma at and follow us on X and LinkedIn. Information about Innate Pharma shares ISIN code Ticker code LEI FR0010331421 Euronext: IPH Nasdaq: IPHA 9695002Y8420ZB8HJE29 Disclaimer on forward-looking information and risk factors This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including “believe,” “potential,” “expect” and “will” and similar expressions, is intended to identify forward-looking statements. Although the company believes its expectations are based on reasonable assumptions, these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those anticipated. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, progression of and results from its ongoing and planned clinical trials and preclinical studies, review and approvals by regulatory authorities of its product candidates, the Company’s commercialization efforts and the Company’s continued ability to raise capital to fund its development. For an additional discussion of risks and uncertainties which could cause the company's actual results, financial condition, performance or achievements to differ from those contained in the forward-looking statements, please refer to the Risk Factors (“Facteurs de Risque") section of the Universal Registration Document filed with the French Financial Markets Authority (“AMF”), which is available on the AMF website or on Innate Pharma’s website, and public filings and reports filed with the U.S. Securities and Exchange Commission (“SEC”), including the Company’s Annual Report on Form 20-F for the year ended December 31, 2022, and subsequent filings and reports filed with the AMF or SEC, or otherwise made public, by the Company. This press release and the information contained herein do not constitute an offer to sell or a solicitation of an offer to buy or subscribe to shares in Innate Pharma in any country. View source version on businesswire.com: Contacts For additional information, please contact: Investors Innate Pharma Henry Wheeler Tel.: +33 (0)4 84 90 32 88 Henry.wheeler@innate-pharma.fr Media Relations NewCap Arthur Rouillé Tel.: +33 (0)1 44 71 00 15 innate@newcap.eu Source: Innate Pharma SA View this news release online at: