On April 9, 2021 Repertoire Immune Medicines, a clinical-stage biotech company decoding the immune synapse to create novel immune therapies for cancer, immune disorders, infectious disease, and other serious diseases, reported the presentation of translational data obtained from applying its proprietary antigen-specific TCR-MHC DECODE platform in its Phase 1 trial evaluating PRIME IL-15 (RPTR-147) in patients with advanced or metastatic solid tumor cancers (Press release, Repertoire, APR 9, 2021, View Source;-PRIME-IL-15-RPTR-147—-in-Advanced-or-Metastatic-Solid-Tumor-Cancers [SID1234577805]). The data will be presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Virtual Meeting Week 1, taking place April 10-15, 2021. PRIME IL-15, the company’s lead investigational therapy, is a novel non-genetically modified, autologous, multiclonal T cell product derived from the patient’s T cell repertoire in the peripheral blood, activated against a curated set of tumor antigens, and armored with an IL-15Fc nanogel. It is being evaluated for a variety of solid tumors.

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In this study, Repertoire Immune Medicines’ applied its proprietary DNA-barcoded pMHC tetramer technology (CIPHERTM) to determine the specificity of its multiclonal T cell product. In addition, bulk sequencing of TCRVβ was performed on tumors pre- and post-treatment and identified product derived CD8+ T cell clonotypes in the post-, but not pre-treatment biopsies. The presentation also details the use of the company’s platform to de-orphan these tumor infiltrating lymphocytes (TIL) of interest, and clone selected TIL TCRs to determine their exact specificities by epitope and HLA.

These translational data demonstrate that rare T cell clones — derived from the peripheral blood — can be amplified and directed to tumor antigens in humans. Further, these findings highlight the unique capability of the company’s DECODE platform to fully decipher the immune synapse by identifying the T cell clones and their cognate antigens by HLA that matter in patients.

Details:

Abstract title: Tracking and Decoding the Antigen Specificity of Peripherally Derived T Cells that Infiltrate into Solid Tumors in patients treated with PRIME IL-15 (RPTR-147)
Session category: Adoptive Cell Therapy (PO.CL06.01)
Date & time: April 10, 2021 from 8:30 a.m. – 12:00 p.m. EDT

On April 9, 2021 Humanigen, Inc. (Nasdaq:HGEN), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, reported positive results from the Phase 1 safety and bioimaging trial of its second Humaneered antibody, ifabotuzumab, in patients with glioblastoma multiforme (GBM) (Press release, Humanigen, APR 9, 2021, View Source [SID1234577804]). In the study, ifabotuzumab demonstrated highly sensitive, specific, and reproducible targeting of the tumor and tumor microenvironment in all patients. The results will be presented as a poster at the AACR (Free AACR Whitepaper) Annual Meeting 2021, held virtually from April 10-15, 2021, and remain available until June 21, 2021.

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The Phase 1 study primarily sought to determine the safety and recommended Phase 2 dose of ifabotuzumab in patients with GBM, the most frequent and lethal primary brain neoplasm, with 5-year survival rates of 10%. It is estimated there are more than 18,000 deaths from brain cancer annually in the United States.1 Ifabotuzumab is a non-fucosylated IgG1κ antibody targeting the EphA3 receptor. EphA3 is a tumor-restricted antigen expressed in the tumor vasculature and tumor stroma of various solid tumors including breast, colon, lung, prostate, melanoma, and GBM. The study showed that, at both doses, ifabotuzumab demonstrated highly sensitive, specific, and reproducible targeting of the tumor and tumor microenvironment in all patients. There were no dose-limiting toxicities observed and all adverse events were readily manageable. Additional studies are planned to evaluate ifabotuzumab as an antibody-drug conjugate in solid tumor patients.

"GBM represents an extremely aggressive form of cancer that has historically eluded effective treatment, and we remain committed to investigating ifabotuzumab as a potential new approach to treat this devastating disease as well as other solid tumors," said Prof. Andrew Scott, Head, Tumor Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Professor, School of Cancer Medicine, La Trobe University, member of the Australian Brain Cancer Mission Strategic Advisory Group, and Principal Investigator of the Phase 1 study. "The positive results of the Phase 1 study, which show ifabotuzumab to be well-tolerated and effective at targeting the EphA3 receptor, support further investigation into ifabotuzumab’s effect on other solid tumors in a Phase 2 study."

The poster, titled "A phase 1 safety and bioimaging trial of ifabotuzumab (KB004) in patients with glioblastoma," will be presented virtually at the AACR (Free AACR Whitepaper) Annual Meeting during the Phase 1 Clinical Trials Session on Saturday, April 10, 2021. The study was led by Principal Investigator Andrew Scott from the Olivia Newton-John Cancer Research Institute in Australia. Funding was provided by Cure Brain Cancer Foundation, the Queensland Government, Austin Health, and Humanigen.

"We are pleased to announce the positive Phase 1 results of ifabotuzumab in patients with gliobastoma multiforme," said Cameron Durrant, MD, MBA, Chief Executive Officer of Humanigen. "There is a tremendous need to advance new therapies for solid tumors, and this trial shows that ifabotuzumab demonstrates great potential. Ifabotuzumab represents an important part of Humanigen’s immuno-oncology arsenal as we advance our pipeline to target a wide-range of cancers, and we are proud to present our findings at this year’s AACR (Free AACR Whitepaper) Annual Meeting."

Details for the upcoming event are below:

AACR Annual Meeting 2021

Virtual abstract presentation viewable starting on Friday, April 9, 2021
Register here: View Sourceregistration/" target="_blank" title="View Sourceregistration/" rel="nofollow">View Source

E-poster presentation
Date: Saturday, April 10, 2021
Link: View Source

On April 9, 2021 Systems Oncology, an AI-based pharmatech company, reported that Dr. Spyro Mousses, CEO and Co-Founder of Systems Oncology, will present at the BMO BioPharma Spotlight Series: Technology-Enabled Drug Discovery on Friday, April 16th at 11.15 AM EST (Press release, Systems Oncology, APR 9, 2021, View Source [SID1234577803]). Systems Oncology will review its unique strategy for leveraging AI-based multi-target discovery, and unveil its transformative RNAi therapeutic platform for creating innovative RNA drugs that can overcome therapy resistance in oncology indications.

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A recording of the panel discussion will be available for approximately four hours following the conclusion of the event and can be accessed under the "News and Events" section of the company’s website at www.systemsoncology.com.

On April 9, 2021 City of Hope, a world-renowned cancer research and treatment center, reported that it will showcase breakthrough research and innovative studies at the first week of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, which will take place virtually from April 10 to 15 (Press release, City of Hope, APR 9, 2021, View Source [SID1234577802]).

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City of Hope scientists will present findings that could one day lead to an effective KRAS inhibitor for solid tumors, innovative chimeric antigen receptor (CAR) T cell therapy for glioblastoma, potent CAR natural killer cell therapy against pancreatic cancer, improved health equity for marginalized communities, better ways to prevent and treat colorectal cancer, and much more.

The multidisciplinary meeting program will highlight the best cancer science and medicine in the world. Last year more than 73,000 people from 140 countries attended AACR (Free AACR Whitepaper)’s first-ever virtual meeting. Some City of Hope research that will be presented at the AACR (Free AACR Whitepaper) meeting is highlighted below.

More competition in KRAS inhibitor space: Revolution Medicine’s RMC-4630
Time: April 10 from 2:05 to 2:15 p.m. EDT
This late-breaking oral presentation led by City of Hope’s Marianna Koczywas, M.D., will address the anti-tumor activity and tolerability of the SHP2 inhibitor RMC-4630 as a single agent in patients with RAS-addicted solid cancers. The first-in-human Phase 1 study demonstrated that RMC-4630 is a potent, selective inhibitor of SHP2, which appears to be an important regulator of growth signals for cancer cells. RMC-4630 exhibited anti-tumor activity in cancers harboring KRASG12C, KRASG12D, NF1 loss of function and BRAF Class 3 mutations. Based on these findings, four targeted therapy combination studies are currently underway, including combinations of RMC-4630 with the KRASG12C inhibitor sotorasib, the checkpoint inhibitor pembrolizumab and the MEK inhibitor cobimetinib.

CAR T cell therapy reshapes tumor microenvironment in glioblastoma
Time: April 12 from 2:05 to 2:15 p.m. EDT
This translational research uses murine models and patient samples to evaluate how CAR T cell therapy reshapes the tumor microenvironment to promote host anti-tumor immune responses in glioblastoma. Christine Brown, Ph.D., deputy director of the T Cell Therapeutics Research Laboratory at City of Hope, and her colleagues look at IL13Rα2-targeted CAR T cells for the treatment of glioblastoma and demonstrate that CAR T cell treatment of mice with glioblastoma alters the tumor immune landscape, activates myeloid cells within tumors and induces innate T cell memory responses. These studies establish that CAR T cell therapy has the potential to reshape the microenvironment of solid tumors, potentially activating innate, adaptive immunity. Cancer Discovery recently accepted this research for publication.

CAR NK therapy directed against pancreatic cancer
Time: April 10, 8:30 a.m. to 11:59 p.m. EDT
This late-breaking poster presentation led by City of Hope’s Michael Caligiuri, M.D., and Jianhua Yu, Ph.D., presents a potent human chimeric antigen receptor (CAR) natural killer (NK) cell therapy against pancreatic cancer. About 60-80% of pancreatic cancer express prostate stem cell antigen. The scientists developed CYTO NK-203 to spontaneously kill both liquid and solid tumors in animal models using human umbilical cord NK cells that are transduced with CAR. The research suggests that this biopharmaceutical may be able to prolong survival against pancreatic tumor cells without side effects, at least in animal models. CYTO NK-203, which was licensed to CytoImmune Therapeutics Inc., is expected to move into clinical trials at City of Hope within 12 months, Caligiuri said.

Neighborhood disadvantage linked to aggressive non-small cell lung cancer
Time: April 10 from 8:30 a.m. to 11:59 p.m. EDT
City of Hope’s Loretta Erhunmwunsee, M.D., looked at the association of neighborhood disadvantage and the biology of aggressive non-small cell lung cancer. Non-small cell lung cancer has a disproportionately higher incidence and mortality rate in marginalized communities, who often reside in neighborhoods with adverse conditions influenced by economic, housing, education, transportation and environmental factors. Researchers looked at 426 non-small cell lung cancer patients treated at City of Hope and found that those who lived in disadvantaged neighborhoods were more likely to have a somatic KRAS mutation — a mutation that is associated with lower survival. This relationship was consistent even when smoking status and pollution were considered and suggests neighborhood disadvantage may be an important determinate of aggressive non-small cell lung cancer biology, possibly explaining why marginalized individuals have worse outcomes.

Predictors of clonal immune responses in colorectal cancer
Time: April 10 from 8:30 a.m. to 11:59 a.m. EDT
Stephen Gruber, M.D., Ph.D., M.P.H., director of City of Hope’s Center for Precision Medicine, studied clinical and epidemiologic predictors of clonal immune responses in colorectal cancer to better understand what causes diverse immune responses. He and his colleagues found that the use of statins and daily aspirin for more than five years prior to when a patient was diagnosed with colon cancer was strongly associated with the quality and behavior of the immune cells (T cells) within the tumor itself. Their research suggests that adaptive immune response may be linked to modifiable factors. Having a better understanding of the mechanisms that regulate immune responses in colorectal cancer may have implications for chemoprevention and immunotherapy.

On April 9, 2021 Novocure (NASDAQ: NVCR) reported 26 presentations on Tumor Treating Fields suggesting broad applicability of Tumor Treating Fields at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021, held virtually from April 10 to April 15, 2021 (Press release, NovoCure, APR 9, 2021, View Source [SID1234577801]). Research spanning seven solid tumor types confirms the anti-mitotic effect of Tumor Treating Fields and further explores downstream effects to identify optimal use of Tumor Treating Fields, including the role of Tumor Treating Fields-induced immunogenic cell death.

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Presentation highlights include research showing the induction of robust anti-tumor immunity by Tumor Treating Fields in glioblastoma, the immunoregulatory role of Tumor Treating Fields on macrophage polarization, the effects of Tumor Treating Fields on DNA damage repair, and replication stress as a pathway to illuminate novel combination therapy options.

"Ongoing research at Novocure and throughout the global scientific community continues to build upon and deepen our understanding of Tumor Treating Fields as we strive to extend survival in some of the most aggressive forms of cancer," said Dr. Uri Weinberg, Novocure’s Chief Science Officer. "We are honored to be a part of the invaluable exchange of scientific information at the AACR (Free AACR Whitepaper) Annual Meeting and are particularly pleased to see an increasing focus on the effect of Tumor Treating Fields on the immune system’s response against cancer."

Presentations from Novocure-sponsored and partner programs include:

(Poster #: CT258) EF-32 (TRIDENT): A pivotal randomized trial of radiation therapy concomitant with temozolomide +/- Tumor Treating Fields (TTFields) in newly diagnosed glioblastoma. W. Shi (Clinical Trials)

(Poster #: LB064) Long-term application of TTFields in anaplastic astrocytoma – a case study. D. Markovic (Clinical Research)

(Poster #: 2635) Contemporary clinical practice guidelines for the management of glioblastoma: an international survey. A. Lawson McLean (Science and Health Policy)

(Poster #: 1065) Concomitant dexamethasone treatment and tumor treating fields induced cell death in glioblastoma. B. Linder (Combination Therapies)

(Poster #: 2634) French health utilities for patients with glioblastoma using TTFields. G. Chavez (Science and Health Policy)

(Poster #: 717) Rapid transformation of TTFields care-delivery during COVID-19 pandemic to optimize treatment of patients with glioblastoma (GBM). P. Frongillo (COVID-19 and Cancer)

(Poster #: 1435) The distribution of Tumor Treating Fields is effected by cell confluence and pores in the membrane. T. Marciano (Experimental and Molecular Therapeutics)

(Poster #: 3070) Lung cancer TTFields treatment planning sensitivity to errors in torso segmentation. H. Ben Atya (Tumor Biology)

(Poster #: 3071) A method for infratentorial structures segmentation for tumor treating fields treatment planning. Y. Glozman (Tumor Biology)

(Poster #: 1692) A novel immunoregulatory role of Tumor Treating Fields (TTFields) on macrophage polarization. B. Brant (Immunotherapy, Preclinical and Clinical)

(Poster #: 1063) Effectiveness of Tumor Treating Fields (TTFields) in combination with sorafenib for treatment of hepatocellular carcinoma in vitro and in vivo. A. S. Davidi (Experimental and Molecular Therapeutics)

(Poster #: 1317) Inovivo: a dedicated system for delivery of therapeutic level Tumor Treating Fields (TTFields) to mice. S. Davidi (Experimental and Molecular Therapeutics)

(Poster #: 1382) Targeting Akt signaling pathway potentiates the antitumor effect of Tumor Treating Fields (TTFields) in vitro. A. Klein-Goldberg (Experimental and Molecular Therapeutics)

(Poster #: 1186) Efficacy of Tumor Treating Fields (TTFields) in mesothelioma is associated with reduced capacity for DNA damage repair. H. Mumblat (Experimental and Molecular Therapeutics)

(Poster #: 279) Transient opening of the blood brain barrier by Tumor Treating Fields (TTFields). C. Tempel Brami (Cancer Chemistry)

(Poster #: 1064) Antiproliferative effects of Tumor Treating Fields (TTFields) in human mesothelioma cell lines. M. Lupi (Combination Therapies)

(Poster #: 1200) Long-duration term TTFields treatment of glioblastoma cells induces cell death. S. Castiglione (New Targets)

(Poster #: 1037) Valproic acid (VPA) combined with Tumor Treating Fields (TTFields) in vitro decreases cellular proliferation and increases clonogenic potential of glioblastoma (GBM) cells. S. Michelhaugh (Combination Therapies)

(Poster #: 1007) Patient-derived metastatic renal carcinoma cells are highly sensitive to Tumor Treating Fields (TTFields) in vitro. S. Michelhaugh (Cellular Responses to Anticancer Drugs)

(Poster #: 2011) Tumor Treating Fields Induce Cellular and Morphologic Changes that Include Disruption of Intercellular Communication Networks in Malignant Pleural Mesothelioma. A. Sarkari (Cell-cell Interactions)

(Poster #: 1678) Induction of Robust Anti-Tumor Immunity by Tumor Treating Fields in Glioblastoma. D. Chen (Immune Response to Therapies)

(Poster #: 3063) Prostaglandin e receptor 3 mediates resistance to Tumor Treating Fields in glioblastoma cells. D. Chen (Radiation Science)

(Poster #: 1051) Targeting replication stress pathway provides an avenue for novel combination therapy options including TTFields plus chemo agents which increase replication stress. N. Karanam (Combination Therapies)

(Poster #: 1975) Tumor Treating Fields Triggers Autophagy Pathway Activation at Primary Cilia to Promote Glioma Cell Survival. P. Shi (Cell Signaling)

(Poster #: 3049) Tumor treating fields induce DNA damage and apoptosis in medulloblastoma. R. Nitta (Pediatric Cancer: Basic Science)

(Poster #: LB023) Drug loaded nanoparticle targeting of pancreatic cancer using tumor treating fields (TTFields). P. Desai (Cancer Chemistry)

About Tumor Treating Fields
Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields is intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a broad range of clinical trials across all phases, included four phase 3 pivotal trials in a variety of tumor types. To date, more than 18,000 patients have been treated with TTFields.