On August 12, 2019 Harvard University and Merck are reported a collaboration that will provide significant research funding for up to four years to support immuno-oncology research led by Arlene Sharpe, MD, PhD, at Harvard Medical School (HMS) (Press release, Merck & Co, AUG 12, 2019, View Source [SID1234538604]). Sharpe, the George Fabyan Professor of Comparative Pathology and chair of the HMS Department of Immunology, will collaborate with researchers at Merck on a major project aiming to discover novel aspects of the immune system that may be targeted in future treatments for cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This collaborative project aims to discover and validate novel regulators of immune responses," said Dr. Sharpe. "Immunotherapies such as checkpoint inhibitors have revolutionized the treatment of cancer, but my lab is deeply interested in understanding why some patients do not respond or develop resistance to those interventions. My hope is that by defining mechanisms that inhibit immune responses to tumors, we will identify very important druggable targets and new approaches to improve cancer immunotherapy."

The funding will support the work of scientists in the lab of Dr. Sharpe, who is a renowned leader in the field of tumor immunology. She is a member of the National Academy of Sciences and the National Academy of Medicine, and the recipient of numerous awards including the Warren Alpert Foundation Prize in 2017 for her contributions to the discovery of the PD-1 pathway.

"Crucial insights into patient responses and outcomes may be gained through the study of fundamental biological mechanisms," said Isaac Kohlberg, Harvard’s Chief Technology Development Officer and Senior Associate Provost. "The complexity and promise of immuno-oncology presents a prime opportunity for Harvard’s top scientists to advance discovery through an academic-industry collaboration. Through this project, the Sharpe Lab is setting its sight on innovations that may contribute to dramatic improvements in patient care."

Under the agreement spearheaded by Harvard’s Office of Technology Development, Merck will have the option to negotiate an exclusive license to innovations arising from the research collaboration to develop these discoveries toward potential treatments for patients.

"Collaboration with leading scientific groups is an integral part of Merck’s discovery strategy," said Dr. Nick Haining, vice president for oncology discovery at Merck Research Laboratories. "We look forward to working with Dr. Sharpe’s team to investigate new ways to harness the immune system for therapeutic advances."

On August 12, 2019 Saul Priceman, Ph.D., City of Hope assistant professor in the Department of Hematology & Hematopoietic Cell Transplantation, and his research team have received a $9.28 million award from the California Institute for Regenerative Medicine (CIRM) to support a chimeric antigen receptor (CAR) T cell phase 1 clinical trial for the treatment of women with HER2-positive breast cancer that has spread to the brain (Press release, City of Hope, AUG 12, 2019, View Source [SID1234538603]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

HER2 refers to a protein – human epidermal growth factor receptor-2 – which is found on the cell surface of breast cancer cells and drives cancer progression. About 20% of breast cancer patients are HER2-positive, according to the American Cancer Society.

The trial, which opened for enrollment in the fall of 2018 and whose lead clinical investigator is Jana Portnow, M.D., City of Hope associate clinical professor in the Department of Medical Oncology & Therapeutics Research, is testing the safety and effectiveness of the CAR T cell therapy for breast cancer patients with brain metastases who are not effectively being controlled with other therapies. It is estimated that nearly half of all women with HER2-positive breast cancer will eventually develop brain metastases.

"Our team’s goal is to develop a novel therapy for breast cancer patients with brain metastases who currently have no other effective treatments," Priceman said. "This is a beautiful example of how early support from private donors and foundations helped to develop a therapy and initiate a trial we were desperate to bring to patients, and now this CIRM award funds the entire clinical trial and helps to leverage the knowledge gained here to further advance this therapy."

CAR T cells are a cell-based type of immunotherapy in which a patient’s own T cells are reprogrammed to actively seek out and destroy cancerous cells. For this trial, the patient’s T cells will be isolated from the blood and genetically engineered to express a CAR that allows these immune cells to target and eradicate HER2-positive cancer cells. Patients receive CAR T cells directly to the ventricles of their brains, which is an administration route that was first attempted successfully at City of Hope. City of Hope patents covering the HER2 CAR were licensed to Mustang Bio in 2017.

City of Hope, a recognized leader in CAR T cell therapies, has treated more than 350 patients since its CAR T program started in the late 1990s. The institution continues to have one of the most comprehensive CAR T cell clinical research programs in the world – it currently has 20 ongoing CAR T cell clinical trials, and has just initiated trials for patients with solid tumors, including prostate cancer.

The trial’s key investigators include City of Hope’s Stephen J. Forman, M.D., director, T Cell Therapeutics Research Laboratory and the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation; Christine Brown, Ph.D., deputy director, T Cell Therapeutics Research Laboratory and the Heritage Provider Network Professor in Immunotherapy; and Behnam Badie, M.D., chief of City of Hope’s Division of Neurosurgery and Heritage Provider Network Professor in Gene Therapy. The award also includes City of Hope’s Russel Rockne, Ph.D., Vanessa Jonsson, Ph.D., Ammar Chaudhry, M.D., as well as collaborations with University of Southern California’s Peter Kuhn, Ph.D., and California Institute of Technology’s Lior Pachter, Ph.D.

CIRM funded early preclinical work related to this study, which was important in optimizing the therapy for the eventual Food and Drug Administration approval for permission to start a clinical trial. City of Hope also highlights Eli Khouri, Steve Meringoff, Zach Horowitz, Jody and Gary Marsh, The Kenneth T. and Eileen L. Norris Foundation and Gateway for Cancer Research for their support of this program.

On August 12, 2019 LineaRx, Inc. ("LineaRx"), a majority-owned subsidiary of Applied DNA Sciences, Inc. (NASDAQ: APDN) ("Applied DNA" or the "Company") reported that, in a decision rendered on August 7, 2019, the Centers for Medicare and Medicaid Services (CMS) approved chimeric antigen receptor (CAR) T-cell therapies that fit the CMS criteria for Medicare beneficiaries nationwide (Press release, LineaRx, AUG 12, 2019, View Source [SID1234538602]). LineaRx believes its unique method of manufacturing DNA is well poised to benefit from the increasing demand for nucleic-acid dependent therapies, like CAR T, as biotechnology companies pursue their gene and cell therapies with reimbursement assured by the CMS decision.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CAR T-based treatments involve extracting and genetically altering a patient’s T cells to attack a protein on the surface of cancer cells. The cells are then infused back into the patient. All approved CAR T and other redirected cell therapies are manufactured using DNA that is bacterially derived and then delivered to the patient’s T cells by a virus. Such plasmids-based treatments require about three weeks to grow and are acknowledged to have the potential for unintended side-effects. LineaRx offers a cleaner, potentially higher-performing alternative to plasmid DNAs with linear DNAs produced by PCR (Polymerase Chain Reaction) that are used to reprogram CAR T cells. Applications for redirected cells are broadly anticipated with more than 850 trials globally listed on clinicaltrials.gov.

"The oncology community has greeted CAR T cell therapy with extraordinary enthusiasm, but the use of these novel therapies to combat cancer has been constrained by pricing and reimbursement. With the CMS decision, redirected cell therapies are now a permanent part of the toolbox of modern medicine, and with LineaRx, we believe we have a more desirable manufacturing process than plasmids, that will enable biotech companies to accelerate their commercialization efforts," stated Dr. James Hayward, president and CEO of LineaRx. "With the LineaRx ability to provide massive ultrapure DNA with shorter lead times than plasmids, its manufacturing technology should enable gene therapy companies to shorten time-to-market for their therapies and in a much more cost-efficient manner. Patients will also benefit by a more rapid turnaround. Moreover, we believe that our recent acquisition of Vitatex, which just closed last week, facilitates our development of redirected cell therapies by enabling us to study the lymphocytes that we capture alongside the circulating tumor cells from the blood of cancer patients. We believe these studies will guide us toward optimal design of the engager that allows CAR T cells to recognize their host’s cancer at a molecular level."

Full text of CMS decision: Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG-00451N)

On August 12, 2019 Zai Lab Limited (NASDAQ: ZLAB), a Shanghai-based innovative commercial stage biopharmaceutical company, and Novocure (NASDAQ: NVCR), a global oncology company with a proprietary platform technology called Tumor Treating Fields, reported that the China National Medical Products Administration (NMPA) granted Innovative Medical Device Designation for Optune, a Tumor Treating Fields delivery system that uses electric fields tuned to specific frequencies to disrupt cancer cell division, inhibiting tumor growth and causing affected cancer cells to die (Press release, Zai Laboratory, AUG 12, 2019, View Source [SID1234538601]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited that Optune has been granted the Innovative Device Designation as it will allow our team to accelerate dialogue with the NMPA and bring us closer to commercializing Optune in China," said Dr. Samantha Du, Founder and CEO of Zai Lab. "Our launch in Hong Kong has provided valuable insight into the impact that this device can have on patients with GBM, which is an area of high unmet clinical need in China and globally. We look forward to working closely with the NMPA as Optune advances through the regulatory process in China."

The Innovative Device Designation allows Zai Lab to take advantage of an expedited approval procedure for Optune that offers opportunities for pre-consultation with and input from the NMPA throughout the approval process. Novocure granted Zai Lab an exclusive license for Tumor Treating Fields, including the brand name Optune, in Greater China in September 2018 and Zai Lab successfully launched the product in Hong Kong for the treatment of glioblastoma (GBM) late last year. Novocure markets Optune in the United States, European Union, Japan and certain other countries for the treatment of GBM and the NovoTTF-100L System, another Tumor Treating Fields delivery system, in the U.S. for the treatment of malignant pleural mesothelioma. Tumor Treating Fields is in late stage clinical development for four solid tumor indications including non-small cell lung cancer, brain metastases, pancreatic and ovarian cancers. Tumor Treating Fields was included and recommended with Level 1 evidence as a treatment for GBM in China’s Glioma Treatment Guideline published in 2018.

"We are committed to bringing Optune to as many patients who may benefit as possible," said Novocure’s Executive Chairman Bill Doyle. "Zai Lab has been an excellent partner as we strive to extend survival in some of the most aggressive forms of cancer by developing and commercializing Tumor Treating Fields therapy. We are pleased that together with our partners at Zai Lab we are one step closer to commercializing Optune in China."

About Tumor Treating Fields

Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and causing affected cancer cells to die. Tumor Treating Fields does not stimulate or heat tissue and targets dividing cancer cells of a specific size. Tumor Treating Fields causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. Tumor Treating Fields is approved in certain countries for the treatment of adults with glioblastoma and mesothelioma, two of the most difficult cancer types to treat. The therapy shows promise in multiple solid tumor types – including some of the most aggressive forms of cancer.

On August 12, 2019 TScan Therapeutics reported the publication in the scientific journal Cell describing the invention of a breakthrough technology that enables the rapid and unbiased discovery of the physiologic targets of any T cell (Press release, TScan Therapeutics, AUG 12, 2019, View Source [SID1234538600]). This work is the foundation for development efforts at TScan Therapeutics to discover new TCR immunotherapies for cancer and infectious disease. The work described in the Cell article is based on research and discoveries by scientific founders of TScan, Stephen Elledge, PhD of Harvard Medical School and Tomasz Kula, PhD. TScan Therapeutics has an exclusive world-wide license to use the technology to discover and develop novel therapies based on T cell receptors (TCRs).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Although cytotoxic T cells are the primary cells in the human immune system that are responsible for detecting and eliminating cancer cells, there has been no thorough and systematic way to determine what peptide antigens those T cells are recognizing until now," commented Dr. Elledge. "The TScan technology provides a method to better understand the natural T cell response to cancer and how we might use that information to design safer and more effective T cell therapies."

Dr. Tomasz Kula, a recent graduate from the Elledge Laboratory at Harvard Medical School, worked with Dr. Elledge and his team to develop the TScan technology. In the Cell paper, researchers from the Elledge Laboratory describe how the technology can be used in the areas of cancer and infectious disease to discover new targets for TCR therapy. The authors also demonstrate how tumor-derived TCRs can be fully characterized to reveal both their primary targets and any potential off-targets that may affect their safety profile as therapeutics.

"The TScan technology has advantages over previous approaches to TCR target identification because it relies on natural processes in both the T cells and their target cells to capture physiologically relevant and functional interactions," commented Dr. Kula. "I am excited to now apply this technology to the discovery of new targets for cancer therapy."

"I am thrilled that Tomasz has elected to join the TScan team," commented Gavin MacBeath, PhD, CSO of TScan Therapeutics. "Tomasz and I share the same vision for TCR therapeutics. His ingenuity and insight will be invaluable as we further develop the TScan technology platform and use it to discover and develop life-changing therapies for patients."

The paper, T-Scan: A Genome-wide Method for the Systematic Discovery of T Cell Epitopes, was published online in the Journal Cell by Tomasz Kula, Mohammad H. Dezfulian, Charlotte I. Wang, Kai W. Wucherpfennig, Herbert Kim Lyerly, Stephen J. Elledge.

Having recently graduated from the Elledge lab, Dr. Kula has joined TScan Therapeutics. Both Stephen Elledge, Professor of Genetics at Harvard Medical School and Kai Wucherpfennig, Professor of Cancer Immunology and Virology at Dana-Farber Cancer Institute and co-author on the Cell paper, are actively engaged with TScan Therapeutics as members of the Scientific Advisory Board.