Active Biotech’s partner NeoTX presents new data at AACR demonstrating that ANYARA enhances the efficacy of checkpoint blockade in preclinical models of cancer

On April 12, 2018 Active Biotech (NASDAQ STOCKHOLM: ACTI) reported that its partner NeoTX Therapeutics Ltd. will present new data for ANYARA (Naptumumab Estafenatox) at the Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago on April 14-18, 2018 (Press release, Active Biotech, APR 12, 2018, View Source [SID1234525482]). The poster Naptumumab Estafenatox Induces T cells Tumor Recognition, Turning anti-PD1 Unresponsive "Cold" Tumors into "Hot" Responsive Tumors will be presented between 1:00 p.m. and 5:00 p.m. local time on April 16, 2018, at the session "Immune Checkpoints 2". The data to be presented demonstrates a synergistic anti-tumor effect when ANYARA is combined with a PD-1 checkpoint inhibitor in several different tumor models that are marginally responsive to PD-1 inhibition.

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Checkpoint inhibitors are drugs that unleash an immune system attack against tumor cells. It is well established that a key factor that limits the effectiveness of checkpoint inhibition is tumor recognition. ANYARA is a Tumor Targeted Superantigen (TTS) that enhances the ability of the immune system to recognize and kill the tumors and is therefore attractive for combination therapy to enhance the efficacy of checkpoint inhibition.

"We are enthusiastic that our partner NeoTX has been selected to present these important data showing that ANYARA, through its tumor-targeted mode of action, enhances the effect of PD-1 inhibition and thereby potentially increases the clinical benefit of such treatment in the long term," says Helén Tuvesson, CEO of Active Biotech.

A summary of the poster presentation will be published at: View Source!/4562/presentation/9330

About ANYARA

ANYARA is a Tumor Targeting Superantigen (TTS) that enhances the ability of the immune system to recognize and kill tumors. Active Biotech has an agreement with NeoTX Therapeutics Ltd since October 2016 for the global development and commercialization of ANYARA for the treatment of cancer. Clinically, the development of ANYARA has focused on cancer forms with a high medical need. Positive data was reported from clinical Phase 1 and 2/3 studies in lung cancer, renal cell cancer and pancreatic cancer, where ANYARA was studied both as a single agent and in combination with an established tumor therapy in patients with advanced cancer. Preparations for a clinical trial in combination with a checkpoint inhibitor are ongoing.

Lund, April 12, 2018
Active Biotech AB (publ)

For further information, please contact:
Helén Tuvesson, CEO
Tel. +46 46 19 20 95
Email: [email protected]

Hans Kolam, CFO
Tel. +46 46 19 20 44
Email: [email protected]

ImmunoCellular Therapeutics Announces Achievement of Next Key Milestone in Stem-to-T-Cell Research Immuno-Oncology Program

On April 12, 2018 ImmunoCellular Therapeutics, Ltd. ("ImmunoCellular" or the Company) (NYSE American: IMUC) reported that it has been able to verify successful transfer of the selected T cell receptor genetic material into human hematopoietic stem cells (Press release, ImmunoCellular Therapeutics, APR 12, 2018, View Source [SID1234525479]). This milestone represents the next important step in validating the Stem-to-T-Cell approach, and is a key component of the proof-of-concept work for this technology. This achievement is a key next step to begin preclinical testing. ImmunoCellular’s Stem-to-T-Cell technology is designed to stimulate the patient’s immune system to produce an unlimited supply of killer T cells that specifically target and destroy tumor cells with minimal side effects.

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ImmunoCellular Therapeutics Logo. (PRNewsFoto/ImmunoCellular Therapeutics) (PRNewsFoto/IMMUNOCELLULAR THERAPEUTICS)

At the end of 2017, the research team at ImmunoCellular successfully transfected genetic material into human hematopoietic stem cells. That work was the basis for this most recent achievement. Successful completion of this phase of work enables the Company to begin preclinical testing in animals, which, if successful, could allow ImmunoCellular’s Stem-to-T-Cell technology to advance into human clinical testing.

"We are excited to have achieved this critical next milestone in our Stem-to-T-Cell program, and are excited to begin the preclinical animal testing that can lay the foundation for potentially proceeding toward conducting human clinical trials," said Steven J. Swanson, PhD, Senior Vice President, Research. "We and our collaborators are now working to design and implement the necessary animal studies to complete our proof-of-concept work. Our vision is to develop solutions for intractable cancers, extend the lives of cancer patients, and provide hope for a potential cure. We believe that our Stem-to-T-Cell program is potentially a game-changing treatment for cancer, and could be effective in treating many types of cancers."

Anthony J. Gringeri, PhD, President and Chief Executive Officer commented: "We are pleased with the productivity and achievements to date of our research team and the continued generation of scientific validation of our Stem-to-T-Cell program. Continued testing of our novel immuno-oncology technology may elucidate how it can be applied in a real-world therapeutic setting, and lead the way toward conducting clinical trials, including potential exploration of combination with other approaches. From a corporate perspective, we are pleased with our ability to achieve our research goals while continuing to operate in a cost-efficient manner. We are also continuing to explore potential collaborations for our clinical programs and other strategic alternatives for our Company."

About ImmunoCellular’s Stem-to-T-Cell Program

Based on the technology in-licensed from The California Institute of Technology in 2014 ImmunoCellular’s Stem-to-T-Cell program is designed to harness the power of the immune system in highly directed and specific ways to engineer highly antigen-specific tumor killing. At the core of the Stem-to-T-Cell technology is the harvesting of stem cells from cancer patients and then cloning into them T cell receptors that are specific for cancer cells. These engineered stem cells can then be reintroduced into the patient and are pre-programed to produce daughter cells that are antigen specific killer T cells that are capable of identifying, binding to, and killing cancer cells. Because stem cells are immortal, these reengineered stem cells could provide a natural and perpetual source of T cells that can target and destroy cancer cells in the patient.

The Stem-to-T-Cell platform has the potential to address many types of cancer, including both solid and hematological tumors and has the potential to result in a potentially curative therapy for many different types of cancers. The stem cell platform represents a novel and more direct approach to generating killer T cells by using the patient’s stem cells as starting material. Thus, ImmunoCellular’s Stem-to-T-Cell technology shares some similarities with other immuno-oncology technologies, such as CAR-T, and could potentially be used in combination approaches. Unlike CAR-T therapies which deliver a large bolus of active T cells into the patient’s circulation and have been associated with toxicity in some patients, ImmunoCellular’s approach enables a more gradual and measured release of killer T cells and has the potential for lower toxicity while also yielding a more sustained response.

Pulse Biosciences Announces Positive Results from Its First Study Evaluating a Clinical Target at Major Scientific Meeting

On April 12, 2018 Pulse Biosciences, Inc. (Nasdaq:PLSE) reported clinical efficacy results of its first multi-center study of Nano-Pulse Stimulation (NPS) technology for the treatment of seborrheic keratosis lesions (SKs) in humans (Press release, Pulse Biosciences, APR 12, 2018, View Source [SID1234525290]). The findings will be featured at the 2018 American Society for Laser Medicine and Surgery (ASLMS) Annual Conference to be held in Dallas on April 11-15, 2018. The company also will present data from the first-in-human clinical study of NPS dose-response effects. These definitive studies establish the foundation for future therapeutic applications of NPS across a range of benign and cancerous skin growths.

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"We were pleased that histology results and clinical findings from the dose response study were predictive of the high lesion clearance rates observed in our first controlled study of a seborrheic keratosis treatment"

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In the clinical trial of SK elimination using the novel, non-thermal NPS technology, seborrheic keratosis lesion reduction assessments of a single, localized SK treatment showed that 82% of 174 treated lesions were rated as clear or mostly clear after 106 days in 58 adult patients. An independent, blinded photographic review of lesion images scored 71% of lesions as clear or mostly clear. Patients rated 78% of lesion outcomes as satisfied or mostly satisfied, closely mirroring investigator ratings.

Thomas Rohrer, MD, a leading dermatologic and Mohs skin cancer surgeon in Boston, MA will present study results on Friday, April 13 at 4:37pm CST in a talk titled First Clinical Use of Non-Thermal Nano-Pulse Stimulation to Eliminate Seborrheic Keratosis Lesions. "These impressive results demonstrate the reliable removal of SK lesions with a single treatment using NPS technology," said Dr. Rohrer. "Pulse’s NPS technology has made a significant leap from very promising pre-clinical results to its first successful application in the removal of a common benign skin lesion with consistent results observed at each of the four top medical centers participating in the study. This unique mechanism of action of non-thermal NPS shows great potential for treating a range of benign and non-benign skin lesions."

In addition to Dr. Rohrer, other investigators in the SK trial included dermatologist George Hruza, MD, a Mohs skin cancer surgeon in St. Louis, MO; facial plastic surgeon James Newman, MD, Chief of Plastic Surgery at Premier Plastic Surgery Clinics in the San Francisco Bay Area, CA; and dermatologist Brian Zelickson, MD of Minneapolis, MN, who is widely recognized for his research in skin tissue effects related to energy-based devices.

The second publication of Pulse Biosciences research at the energy-based science and medicine conference was conferred the ASLMS Best of Basic Science and Translational Research Award. The winning paper is titled A Dose-Response Study of a Novel Non-Thermal Method of Selectively Modifying Cellular Structures in Skin with Low Energy Nanosecond Electrical Stimulation. Clinical results showed that NPS demonstrates a non-thermal mechanism for targeting cellular structures with very low-grade inflammation that does not affect the viability of the non-cellular dermal tissue across a wide range of energy levels as evaluated by clinical and histological responses observed in human skin. This research will be presented on Friday, April 13 at 10:05am CST.

According to dermatopathologist Dr. Mehregan, "Our dermatopathology lab analyzed over 200 biopsy samples from NPS-treated human skin and observed a pattern of unique cellular-effects that spared the non-cellular dermis at most energy doses. These basic tissue findings demonstrate real promise for clinical studies of multiple future clinical applications."

Publication co-authors included plastic surgeon David Kaufman, MD, Folsom, CA; Michelle Martinez, RN, BSN, of Kaufman Plastic Surgery in Folsom, CA; Brian Zelickson, MD; David Mehregan, MD, of Detroit and Monroe MI; and Pulse Biosciences contributors Richard Nuccitelli, PhD, Edward Ebbers, and Lauren Jauregui.

"We were pleased that histology results and clinical findings from the dose response study were predictive of the high lesion clearance rates observed in our first controlled study of a seborrheic keratosis treatment," said Ed Ebbers, Vice President and General Manager of Dermatology at Pulse Biosciences. "These impressive safety results and robust SK efficacy rates increase our confidence in future planned study treatments of other benign lesions, such as keloids and warts, and non-benign skin lesions."

"The presentation of our initial NPS clinical data at the prestigious ASLMS annual meeting is an important milestone for our dermatology program and Pulse Biosciences, as we continue to build the evidence in support of NPS as a unique and compelling treatment modality across a number of applications," added Darrin Uecker, President and CEO of Pulse Biosciences.

For more information: NPS study data presented at 2018 ASLMS Annual Meeting
View Source

About the SK Study

Fifty-eight (58) adult subjects in four clinical centers were required to have at least four (4) off-face lesions within study criteria for size, and a clinical diagnosis of SK. A local anesthetic was injected prior to treatment with the NPS device. Three lesions were treated in a single session, and one lesion was left untreated as a control. Subjects returned five times over a 106-day period for physician assessment of SK lesions and the cosmetic appearance of treated areas.

About Seborrheic Keratoses

Seborrheic keratosis (SK) typically appears as a raised skin lesion with a waxy, scaly texture that can vary in color from light tan to dark brown or black. It affects more than 80 million people in the United States and is often associated with aging skin. A recently published study in the Journal of Clinical and Aesthetic Dermatology found that 61% of patients took action to hide, disguise, or distract attention from their SK lesions. The published study also noted that 86% of SK sufferers were somewhat or extremely interested in a removal treatment in a dermatologist’s office and willing to pay a reasonable out-of-pocket fee. Leading clinicians generally agree that the effective treatment of SK lesions with a non-surgical and nonthermal procedure represents a highly desired alternative to patient inaction due to limitations of existing treatments.

City of Hope Scientists Present New Cancer Research at the American Association for Cancer Research Conference

On April 12, 2018 City of Hope, a world-renowned independent research and treatment center for cancer and diabetes, reported that it will highlight a variety of basic research and population studies at the annual meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) at Chicago’s McCormick Place April 14-18 (Press release, City of Hope, APR 12, 2018, View Source [SID1234525289]).

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City of Hope will highlight basic research at American Association for Cancer Research (AACR) (Free AACR Whitepaper) at Chicago’s McCormick Place April 14-18.

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The AACR (Free AACR Whitepaper) meeting, which will host an anticipated 22,000 representatives from academia, industry, government and advocacy organizations from across the globe, highlights the best cancer science and medicine from institutions all over the world.

"The AACR (Free AACR Whitepaper) meeting draws physicians, scientists, nurses, patients, advocates and others in the field of cancer research together to discuss the most promising breakthroughs in cancer diagnosis, prevention and treatment," said Michael A. Caligiuri, M.D., president, City of Hope National Medical Center, Deana and Steve Campbell Physician-in-Chief Distinguished Chair and AACR (Free AACR Whitepaper) president. "City of Hope physicians and scientists will share their discoveries and expertise with colleagues in the cancer field, who share a passion for finding better cures for cancer patients."

Symposia and poster sessions will feature City of Hope studies on leading-edge cancer treatment and research. Highlighted presentations include:

AACR Presidential Address on the human immune system, from bench to bedside

Caligiuri will give a presentation titled "Human natural killer cells: From biology to CARs (chimeric antigen receptors) in the clinic" on Sunday, April 15, at 5:30 p.m. in Room W196 – McCormick Place West (Level 1). The talk will detail 25 years of Caligiuri’s work on the body’s natural killer cells, from their development to their role in surveying the body to protect against cancer and infection to their modification for re-entry into the clinic as CAR NK cells. For this work as well as for his commitment to advancing cancer health disparities research and promoting the collection and use of clinical samples, Caligiuri was recently elected to the 2018 Class of Fellows of the AACR (Free AACR Whitepaper) Academy. The academy recognizes and honors distinguished scientists whose major scientific contributions have propelled significant innovation and progress against cancer.

City of Hope doctors and scientists to speak in symposiums

Behnam Badie, M.D., City of Hope chief of the Division of Neurosurgery and director of the Brain Tumor Program, will speak at a session that provides an overview of recent advances in CAR T cell therapy and discusses scientific and regulatory challenges related to the clinical development of CAR T therapy for solid tumors. The session takes place on Monday, April 16, 10:30 a.m. – 12:15 p.m., in Room S401bcd – McCormick Place South (Level 4).

Rick Kittles, Ph.D., associate director of health equities in the City of Hope Comprehensive Cancer Center and professor/director, Division of Health Equities, in the Department of Population Sciences, will participate in a major symposium that discusses racial/ethnic disparities in cancer outcomes, and how recent studies suggest that the development of racial/ethnic-specific cancer targeted treatments, diagnostic assays and response profiles might contribute to the elimination of racial/ethnic disparities in cancer outcomes on Tuesday, April 17, from 10:30 a.m. to 12:30 p.m. in Room S106 – McCormick Place (Level 1).

Markus Müschen, M.D., Ph.D., professor and chair, City of Hope Department of Systems Biology and the Norman and Sadie Lee Foundation Endowed Professor, and Jaewoong Lee, Ph.D., assistant research professor in City of Hope’s Department of Systems Biology, will discuss how CD25 enables BCR- and TCR-signaling and represents a therapeutic target in lymphoblastic malignancies as part of a minisymposium defining new immunotherapeutic targets through deep molecular characterization. The session takes place on Monday, April 16, from 3:00 to 5:00 p.m. in Room S100 (Grand Ballroom) – McCormick Place South (Level 1).

Black women’s knowledge of breast cancer and hair product-related risk

Dede Teteh, a post-doctoral fellow in City of Hope’s Division of Health Equities, will present research on the Cost of Beauty project, a community-based participatory research study led by co-principal investigators Phyllis Clark, Eudora Mitchell and Susanne Montgomery, Ph.D. The study examines the potential role of hair products in breast cancer etiology in African American, African and Caribbean black women. Hair products were collected from locations frequented by black women and hair stylists, and the Environmental Working Group’s Skindeep© database was used to evaluate ingredient toxicity. Key informant interviews, focus groups and a survey were then used to assess participants’ knowledge about breast cancer and hair product-related risks.

The study found that all 54 products evaluated from local hair salons contained hazardous ingredients. Fourteen of the ingredients had an overall high hazard rating between 7-10 (with 10 indicating very high levels of toxicity). The potential harmful effects of these chemicals include cancer and endocrine disruption, while some act as reproductive system toxicants. The study included 211 women, most of whom had a college or graduate degree, were more knowledgeable about the diagnosis and treatment of breast cancer (46 percent) than about hair product-related risk (40 percent).

"This study is adding to the dialogue on the impact of personal care products on black women’s health," Teteh said. "We encourage our participants to read their product labels, know what is in the products they use and promote the manufacture of kitchen products using safe ingredients."

Exercise alleviates inflammation-related biomarkers in breast cancer survivors

According to the most current U.S. census, there are about 3.1 million breast cancer survivors in the United States. Although advances in breast cancer therapy have greatly improved survival, successful treatment often comes at a cost, including metabolic disease. Survivors also experience an increase in inflammatory conditions, which cause chronic pain, swelling and other health problems. Research has shown exercise may help combat these and other health conditions, including cardiovascular disease, diabetes and cancer recurrence.

Jessica Clague DeHart, Ph.D., assistant professor, in the Division of Biomarkers of Early Detection and Prevention in City of Hope’s Department of Population Sciences, initiated a feasibility study of a community-based exercise intervention among breast cancer survivors to look at the change in inflammatory biomarkers.

Aditi Vyas, Ph.D., a postdoctoral fellow on her team, analyzed their gene expression profiles, before and after exercise, to help identify adverse molecular events that can be potentially reversed through exercise. The team recruited 50 sedentary, postmenopausal estrogen-receptor positive (ER+) breast cancer survivors, and randomized them into exercise and control groups. Participants in the exercise group were enrolled into an exercise intervention program (Curves), which involved 30-minute circuit-centered exercises performed under trained supervision, three times a week, for 16 weeks. Participants’ body measurements were recorded and blood samples were taken for molecular analysis from all participants, before and after the study.

The results show that 7 of the 10 measured inflammatory markers that can cause health problems decreased in the exercise group compared to the control group. For example, on average, C-reactive protein (CRP) as well as Interleukin-6 were found to be 30 percent and 21 percent lower, respectively, in the post-intervention samples from the exercise group, when compared to the control group. Moreover, a greater number of women in the exercise group showed an overall decrease in pro-inflammatory markers such as IL-6, CRP and IL-8 when compared to the control group. For instance, 71 percent of the women who exercised had reduced levels of IL-8 after intervention when compared to 36 percent of women in the control group.

The gene expression profiling results for the exercise group showed 197 differentially expressed genes post-intervention when compared to the gene expression at the start of the study. Genes involved in inflammatory response such as IF127, CD177 and others were inhibited in response to the exercise intervention.

"In summary, our results indicate that moderate levels of exercise could potentially be useful in alleviating inflammation and stress-related biomarkers in breast cancer survivors," Vyas said.

A citrus ingredient slows the growth of breast cancer cells

Breast cancer is the second leading cause of cancer-related deaths in women in the U.S. Unfortunately, only a few therapeutic strategies are effective in breast cancer treatment, and they are often toxic to healthy cell types. Therefore, there is a need to identify newer strategies that can supplement the existing ones. Studies have shown that phytochemicals, which are plant-derived bioactive components, have anticancer properties and exhibit minimal toxicity to healthy tissue.

Sharad S. Singhal, Ph.D., a professor in City of Hope’s Department of Medical Oncology & Therapeutics Research and Beckman Research Institute, and his team used 2′-Hydroxyflavanone (2HF), a constituent of citrus fruits, and breast cancer cell lines to conduct experiments in vitro. Initial studies demonstrated that 2HF effectively suppressed the growth of breast cancer cells, and researchers decided to investigate the anticancer effects of 2HF in animal models.

"The study showed that 2HF significantly slowed the growth of breast cancer cells by initiating cell death and at the same does not affect growth of normal cells," Singhal said.

Next steps for the research include studying the molecular mechanisms that are involved in 2HF’s stopping breast cancer cells from multiplying, as well as combining 2HF with chemotherapeutic agents currently used for breast cancer treatment to measure their effectiveness.

"There is a critical need to identify potent compounds that can kill cancer cells and/or enhance the efficacy of chemotherapies," Singhal said. "Therefore, the long-term goal of the lab is to develop clinically effective adjuvant for treatment of breast cancer."

Gritstone Oncology to Present First Data Bridging Tumor Antigen Identification and Potent Immunotherapy Delivery in Primates at 2018 AACR Annual Meeting

On April 12, 2018 Gritstone Oncology, a personalized cancer immunotherapy company, reported that preclinical data highlighting the company’s tumor-specific neoantigen (TSNA) identification platform, EDGE (Epitope Discovery in cancer GEnomes), and a novel, potent TSNA delivery approach will be presented during two poster presentations at the 2018 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. The meeting is being held April 14-18, 2018 in Chicago (Press release, Gritstone Oncology, APR 12, 2018, View Source [SID1234525288]).

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Gritstone Oncology will present prediction data from EDGE demonstrating its ability to select tumor-specific neoantigens that have generated anti-tumor immune responses in humans. In an analysis of independently validated, tumor-relevant T cell responses against neoantigens (including from the US National Cancer Institute), EDGE identified, with good specificity, the majority of neoantigens eliciting a CD8+ T cell response in patients with cancer.

Further, the company will present the first preclinical data, including in non-human primates (NHP), highlighting a potent immunotherapy approach to deliver selected TSNA to patients. The delivery approach comprises a chimpanzee adenoviral vector (ChAdV) for the prime immunization, and a self-replicating, synthetic viral RNA vector (srRNA) for repeated boost immunizations. In preclinical NHP studies, delivery of selected antigens using this sequential (heterologous) prime/boost immunization approach, showed a quick onset of immune activation with induction of high numbers of antigen-specific T cells. In addition, co-administration of anti-CTLA4 further enhanced both the number and function of the elicited T cells, suggesting the system’s potential in combination with checkpoint inhibitors.

"In patients with solid tumors, the generation of a very large number of tumor neoantigen-specific CD8+ T cells is one of the major challenges associated with today’s immunotherapies," said Andrew Allen, M.D., Ph.D., co-founder, president and chief executive officer of Gritstone Oncology. "To leverage the neoantigens selected by EDGE, we have developed a potent immunotherapy regimen, which has produced high level CD8+ T cell responses in NHP. Historically, such models have been highly predictive of immune responses observed in humans, and these data support our plans to initiate clinical trials in in the second half of 2018. We are excited to be presenting our research at this year’s AACR (Free AACR Whitepaper) meeting, demonstrating the applicability of our integrated platform for the development of personalized immunotherapies for difficult-to-treat-cancers."

Abstract Title: A novel heterologous prime boost vaccine system drives tumor specific and potent CD8 T cell responses for cancer immunotherapy

Date & Time: April 15, 2018 from 1:00 to 5:00 p.m. CT

Abstract Findings: Gritstone Oncology has developed a potent heterologous prime/boost immunization approach to deliver predicted TSNAs to patients, which is comprised of a replication incompetent chimpanzee adenoviral vector (ChAdV) for the prime vaccination and a self-replicating, synthetic viral vector (srRNA) for repeated boost vaccinations. In a preclinical model, immunization with either vector resulted in strong antigen-specific CD8 T-cell responses and provided a statistically significant survival advantage to tumor bearing mice when compared to untreated mice. The potency was also tested in a non-human primate model, demonstrating quick onset of T-cell responses one week post ChAdV prime vaccination, with peak T-cell responses at two to three weeks and effectively boosted by the srRNA vector. In addition, co-administration of anti-CTLA4 with the vaccine demonstrated enhanced vaccine-induced immune response.

Abstract Title: Antigen identification for cancer immunotherapy by deep learning on tumor HLA peptides

Date & Time: April 18, 2018 from 8:00 a.m. to 12 p.m. CT

Abstract Findings: Using a large dataset of tumor transcriptomes and immunopeptidomes, Gritstone Oncology has trained a deep learning model (EDGE) to predict the presentation of HLA peptides on tumor cells. The model was tested on HLA presented peptides from held-out tumor samples and demonstrated an approximately 10-fold improvement in positive predictive value compared to standard tools. The model was also tested for its ability to predict neoantigens recognized by T-cells and included the majority (16/23, 70%) of validated neoantigens from an independent test set in a putative 20-mutation personalized immunization.