Harnessing T-cell 'stemness' could enhance cancer immunotherapy

Medical Xpress | March 28, 2019

A new study led by scientists in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI) sheds light on one-way tumors may continue to grow despite the presence of cancer-killing immune cells. The findings, published March 29, 2019, in Science, suggest a way to enhance the effectiveness of immunotherapies for cancer treatment. NCI is part of the National Institutes of Health. Dying cancer cells release the chemical potassium, which can reach high levels in some tumors. The research team reported that elevated potassium causes T cells to maintain a stem-cell-like quality, or "stemness," that is closely tied to their ability to eliminate cancer during immunotherapy. The findings suggest that increasing T cells' exposure to potassium—or mimicking the effects of high potassium—could make cancer immunotherapies more effective. "This study helps us better understand why cancer immunotherapy works the way it does," said Nicholas Restifo, M.D., of NCI's CCR, who led the research team. "It could also point the way toward generating better and more long-lasting responses to these treatments."

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The estimated re-admission costs to the healthcare system for COPD are over $49 billion. 1 In the US, hospital re-admissions for all COPD patients within 30 days occur in 22% of cases. 2 CMS is taking control of reimbursement by imposing fines and denying reimbursement for recurrent re-admissions of several diagnoses including COPD. With COPD re-admissions becoming more costly for hospitals, a more cost effective way must be devised to treat moderate to severe COPD in the home, thus reducing exacerbations and frequent hospital re-admissions. Community Surgical Supply (CSS), a mid-atlantic home medical equipment company, has created a program to reduce re-admissions for severe chronic respiratory failure/COPD patients.

Spotlight

The estimated re-admission costs to the healthcare system for COPD are over $49 billion. 1 In the US, hospital re-admissions for all COPD patients within 30 days occur in 22% of cases. 2 CMS is taking control of reimbursement by imposing fines and denying reimbursement for recurrent re-admissions of several diagnoses including COPD. With COPD re-admissions becoming more costly for hospitals, a more cost effective way must be devised to treat moderate to severe COPD in the home, thus reducing exacerbations and frequent hospital re-admissions. Community Surgical Supply (CSS), a mid-atlantic home medical equipment company, has created a program to reduce re-admissions for severe chronic respiratory failure/COPD patients.

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DIAGNOSTICS

Oxford BioTherapeutics Announces Research Collaboration with ImmunoGen to Develop Novel Antibody-Drug Conjugates

Oxford BioTherapeutics | June 14, 2022

Oxford BioTherapeutics (OBT), a clinical stage oncology company with a pipeline of immuno-oncology and Antibody Drug Conjugate (ADC)-based therapies, today announced a multi-year collaboration to research, develop and commercialize novel, first-in-class ADCs with ImmunoGen (IMGN), a leader in the expanding field of ADCs for the treatment of cancer. The companies will utilize ImmunoGen's linker-payload technology directed to novel targets identified via OBT's proprietary OGAP® discovery platform. The companies will support these R&D efforts through joint funding and by combining their respective proprietary technologies. "I am very enthusiastic about our new partnership with ImmunoGen, a leader in the development of ADCs," said Christian Rohlff, PhD, Chief Executive Officer (CEO) of Oxford BioTherapeutics. "The company's expertise, in combination with the unique targets from our OGAP® database, provides potential to strengthen our respective drug pipelines with novel and highly differentiated ADCs for cancer patients in need of novel therapeutic options." As part of the agreement, OBT will receive an upfront payment from ImmunoGen, reflecting OBT's preclinical programs to be included in the partnership. In addition, once antibodies generated by OBT have been coupled with ImmunoGen's proprietary linker-payload technology, each company will have the opportunity to select one or more development programs to further develop on its own. Each company is eligible to receive milestone payments based on the achievement of pre-specified development, regulatory, and commercial milestones, as well as tiered royalties as a percentage of worldwide commercial sales, with respect to each program selected by the other company. Once a company has chosen a given program, it will be solely responsible for all R&D costs associated with the specific program. "OBT has demonstrated expertise in identifying novel targets for the development of specific antibodies – two key components to generating successful ADCs," said Stacy Coen, ImmunoGen's Senior Vice President and Chief Business Officer. "This expertise, combined with ImmunoGen's portfolio of cancer-killing payloads and linkers, will be instrumental as both companies work to develop novel ADCs designed to address cancers with high unmet need. We look forward to working with OBT as we expand and diversify our investment in ADC research capabilities, deepen our pipeline, and transition to a fully-integrated oncology company." ImmunoGen's portfolio is comprised of next-generation maytansinoid, DNA-acting, and novel camptothecin toxins and proprietary linkers. This collaboration will utilize novel targets identified by OBT combined with ImmunoGen's proprietary toxins and associated linkers. OBT has clinical experience with ImmunoGen's ADC platform and DM4 payload, which is utilized in OBT's lead program OBT076, an ADC currently in clinical trials as a monotherapy, as well as in combination with checkpoint inhibitors, in patients with advanced or refractory solid tumors, including gastric, bladder, ovarian, and lung cancer. About Oxford BioTherapeutics Oxford BioTherapeutics is a clinical stage oncology company based in Oxford, UK; San Jose, CA and Morristown, NJ, USA; with a pipeline of first-in-class immuno-oncology (IO) and antibody-drug conjugate (ADC) based therapies designed to fulfil major unmet patient needs in cancer therapeutics. OBT's lead clinical program, OBT076, an ADC utilizing an Immunogen toxin, initiated expansion in a U.S. Clinical Trial in 2021 in patients with advanced or refractory solid tumors, including gastric, bladder, ovarian and lung cancer, where CD205 is overexpressed. Infiltration of tumors by immunosuppressive cells correlates with adverse outcomes (lower progression free and overall survival), suggesting that this process contributes to the progression of several cancers.

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INDUSTRIAL IMPACT

Versant Ventures Collaborates with AbCellera to Accelerate Drug Development for its Portfolio of Biotech Companies

AbCellera and Versant Ventures | July 28, 2022

AbCellera and Versant Ventures announced a multi-year collaboration to discover therapeutic antibodies for multiple targets selected by Versant’s portfolio of biologics-focused biotechs. Versant and AbCellera already have enabled three of the firm’s stealth-stage companies under previous partnerships. Under the terms of the deal, Versant portfolio companies will have rights to develop and commercialize the resulting therapeutic antibodies. AbCellera will receive research payments from the companies and will be eligible to receive downstream clinical and commercial milestone payments plus royalties on net sales of products. Further terms are not disclosed. "In recent years we have made a series of investments into the next generation of therapeutic antibodies. We are seeing a wave of innovation in the antibody space that is allowing us to add novel functionalities to these molecules. Our partnership with AbCellera will further enable our portfolio companies to pursue these important biologic medicines.” Markus Enzelberger, Ph.D., a partner at Versant “AbCellera’s discovery technology provides a complete solution for antibody therapeutics that unlocks new opportunities and levels the playing field for smaller companies, allowing them to advance programs faster, more efficiently and with a competitive advantage,” said Carl Hansen, Ph.D., CEO and President of AbCellera. “We are excited to deepen our relationship with the Versant team and look forward to helping them continue a strong track record of bringing together breakthrough science, experienced teams, and capital to create bold new biotech companies.” Previously, Versant and AbCellera partnered in separate multi-target deals to enable three of the firm’s stealth-stage companies with new approaches to optimize and expand antibody therapies. These include antibody-focused newcos in the fields of immunology and oncology based in Canada, the U.S. and Europe. About Versant Ventures Versant Ventures is a leading healthcare venture capital firm committed to helping exceptional entrepreneurs build the next generation of great companies. The firm’s emphasis is on biotechnology companies that are discovering and developing novel therapeutics. With $4.2 billion under management and offices in the U.S., Canada and Europe, Versant has built a team with deep investment, operating and R&D expertise that enables a hands-on approach to company building. Since the firm’s founding in 1999, more than 85 Versant companies have achieved successful acquisitions or IPOs. About AbCellera Biologics Inc. AbCellera is a technology company that searches, decodes, and analyzes natural immune systems to find antibodies that its partners can develop into drugs to prevent and treat disease. AbCellera partners with drug developers of all sizes, from large pharmaceutical to small biotechnology companies, empowering them to move quickly, reduce cost, and tackle the toughest problems in drug development.

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MEDICAL

Invenshure Launches MEKanistic Therapeutics™

Invenshure | June 03, 2022

Venture studio Invenshure announces the launch of MEKanistic Therapeutics, a biotechnology company redefining precision oncology. Co-inventors and pioneers in the MEK inhibitor field, Judith Sebolt-Leopold, PhD, and Christopher Whitehead, PhD, MBA, have rationally designed a drug that blocks two, key pathways (EGFR and PI3K) used to signal cancer cell growth, with a single molecule. In preclinical studies, this first-in-class dual inhibitor shows unparalleled tumor shrinkage without the toxicity generally associated with current kinase inhibitors. MEKanistic is using cutting edge computational tools to not only understand how these pathways work, but also design medications that perfectly fit within those sites to inhibit the spread of cancer. We have two unique advantages. First, our lead drug's expanded therapeutic window means dramatically reduced side effects for cancer patients. Second, when it's paired with existing cancer therapies, our drug makes them much more effective, We are excited to partner with Pfizer Global R&D veterans, Drs. Leopold and Whitehead, to propel this important technology forward into clinical trials." Danny Cunagin, CEO of MEKanistic. MEKanistic will be launching a round of funding in the coming weeks to support the translation of our lead candidate (MTX-531) towards IND approval later this year with the anticipation of initiation of Phase 1 clinical trials in early 2023. MTX-531's initial application targets head and neck cancers with 900,000 cases worldwide per year. Ultimately, this drug has possible future applications for colon/rectal, esophageal, pancreatic, and some breast cancers. Our work could potentially impact millions of people each year." Chief Scientific Officer, Dr. Sebolt-Leopold. About Invenshure™ Invenshure is a venture studio that scours university research labs for novel and disruptive technologies ready for commercialization. Invenshure partners with top scientists, physicians, and researchers from the most trusted institutions in healthcare and technology. The company focuses on high-growth sectors including biotech, genomics, healthcare IT, diagnostics, cloud computing technologies, and wireless technologies.

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