On October 12, 2020 Baylor College of Medicine reported that Natural killer T (NKT) cells, a type of immune cells known for their potent anti-cancer properties in murine tumor models, have been developed into a novel form of immunotherapy to treat patients with cancer (Press release, Baylor College of Medicine, OCT 12, 2020, View Source [SID1234568607]).

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Researchers at Baylor College of Medicine and the University of North Carolina at Chapel Hill have genetically modified human NKT cells with a chimeric antigen receptor (CAR) that enables them to specifically recognize and attack neuroblastoma, a form of childhood cancer. Expressed with the CAR is interleukin-15 (IL-15), a natural protein that supports NKT cell survival.

In the study, appearing in Nature Medicine, researchers present interim results from an ongoing clinical trial showing that the modified cells are safe, localize to tumors, and, in one of three patients, induced an objective response with regression of bone metastatic lesions.

Enhancing the tumor-fighting capabilities of NKT cells

The earliest CAR-modified cells were immune T cells. CAR T cells have been proven to be effective in treating certain types of leukemia and lymphoma. However, a number of challenges have been encountered in attempts to treat solid tumors with CAR T cells. Preclinical studies have demonstrated that NKT cells offer a novel approach that may enhance CAR-directed cancer immunotherapy.

"In addition to being able to effectively combat tumors in mouse models, the presence of NKT cells within solid tumors is associated with favorable outcomes in cancer patients," said co-corresponding author Dr. Leonid Metelitsa, professor of pediatric oncology at Baylor and Texas Children’s Hospital and member of Baylor’s Dan L Duncan Comprehensive Cancer Center.

Previous work has shown that NKT cells have a spectrum of anti-tumor activities. For instance, these cells migrate to tumor sites where they kill tumor-associated macrophages, a type of immune cell that can promote tumor growth and metastasis. Moreover, NKT cell activation indirectly promotes an anti-tumor response mediated by two other types of immune cells, NK and T cells.

"We think that NKT cells have substantial potential to serve as valuable contributors to the fight against cancer," said co-corresponding and first author Dr. Andras Heczey, assistant professor of pediatric oncology at Baylor and Texas Children’s and member of the Dan L Duncan Comprehensive Cancer Center. "For the last 10 years, we have been focused on enhancing these cells’ tumor-fighting abilities with the ultimate goal of bringing them to the clinic."

Preparing NKT for clinical trials

The journey to develop NKT cells into a form of immunotherapy involved finding solutions for a number of challenges. For example, NKT cells represent a low percentage of the cells in the blood, so Metelitsa, Heczey and their colleagues developed methods to grow NKT cell populations to clinical scale with high purity.

Although NKT cells can combat tumors in several ways, they all seem to be indirect. "Working with Dr. Gianpietro Dotti at UNC, we gave NKT cells a tool – the CAR – that enables them to attack tumors directly," Metelitsa said. "We also equipped them with IL-15, an additional tool to help them survive in the patient while they fight the tumor."

"The field of CAR cellular immunotherapy for cancer has been focused to date primarily on the manipulation of T lymphocytes," said Dotti, professor and director of cancer cellular immunotherapy at UNC Lindberger Comprehensive Cancer Center. "Based on previous clinical evidence that NKT infiltration within the tumor correlates with favorable clinical outcomes, we decided to leverage this intrinsic property of NKTs and to arm them with an additional bullet – the so-called CAR – to further potentiate their capacity to destroy the tumor."

With all these innovations in hand, the researchers moved on to test CAR NKT cells in patients with neuroblastoma in a clinical trial.

Clinical results

The clinical trial is ongoing, and results from the first three patients with heavily pre-treated, relapsed/refractory metastatic neuroblastoma are presented in this study. The patients were treated with CAR NKT cells, engineered from the patient’s own white blood cells at the Center for Cell and Gene Therapy at Baylor and Texas Children’s. Researchers engineered 95 percent pure NKT cells, a portion of which was armed with CAR-IL15.

"Our initial results show that NKT cells can be expanded to clinical scale with high purity, genetically engineered to express a CAR and IL15, and used to safely treat patients with advanced neuroblastoma," Metelitsa said.

"In addition, we found that CAR-IL15 NKT cells can be detected in the peripheral blood, where they expand postinfusion, traffic to bone metastases and the bone marrow, and exert anti–tumor activity," Heczey said. "We observed an objective response, elimination of at least 50 percent of metastases, in one of the patients."

Dr. Antonio Montalbano and other co-authors from Immunai, a company specializing in single-cell technologies and AI approaches for immunology, applied its state-of-the-art technology platform that allows for the analysis of all genes at the single-cell level in the CAR-NKT patient products. These analyses revealed new information about the heterogeneity of human NKT cells and molecular details of their therapeutic modifications. The researchers discovered nine subsets of NKT cells, and that the CAR receptor seemed to go preferentially to one set identified as cluster 3. Further studies will help understand the implications of these findings.

"Our study shows that it is possible to employ immune cells with natural anti-tumor capabilities and enhance their tumor fighting power with designer synthetic receptors, opening the possibility of applying this strategy to combat hard-to-treat solid tumors," Metelitsa said.

"By leveraging Immunai’s end-to-end platform of artificial intelligence and computational analysis, we were able to zero in on CAR engineered NKT cells from the patients at the single-cell level. The findings from this study are critical toward developing more precise and effective therapies for cancer patients," said Montalbano, genomics technologies lead at Immunai. "We’re looking forward to continuing our research with Baylor with the goal of advancing therapeutic discoveries, accelerating drug development and improving patient outcomes."

The NKT platform developed in this research at Baylor has been licensed to Kuur Therapeutics to advance clinical development.

"The Baylor-Kuur Therapeutics relationship is generating exactly the type of outcomes that we had envisioned at the outset," said Shawn Davis, vice president and chief ventures officer at Baylor. "The modified NKT platform developed in the Metelitsa laboratory is differentiated from other cell therapy platforms, offering novel routes for the treatment of cancers that have posed challenges for immunotherapeutic approaches. The encouraging findings announced today support the potential of NKT platform to provide promising alternatives, particularly for the treatment of solid tumors."

Other contributors to this work include Amy N. Courtney, Simon Robinson, Ka Liu, Mingmei Li, Nisha Ghatwai, Olga Dakhova, Bin Liu, Tali Raveh-Sadka, Cynthia N. Chauvin-Fleurence,Xin Xu, Ho Ngai, Erica J. Di Pierro and Barbara Savoldo. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Texas Children’s Hospital, Immunai Inc. and the University of North Carolina at Chapel Hill.

This work was supported by grants/contracts from Alex’s Lemonade Stand Foundation for Childhood Cancer, Kuur Therapeutics, American Cancer Society, Cookies for Kids’ Cancer Foundation, and the Cancer Prevention and Research Institute of Texas (BCM Comprehensive Cancer Center Training Program, RP160283).

On October 12, 2020 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO) reported that the Company has informed the European Medicines Agency, EMA, about its intention to submit an application for a conditional marketing authorization of melflufen (INN melphalan flufenamide) in the EU, based on the pivotal phase 2 HORIZON study in relapsed refractory multiple myeloma (RRMM) (Press release, Oncopeptides, OCT 12, 2020, View Source [SID1234568301]).

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The decision to submit an application for conditional approval has been grounded on an in-depth analysis of the regulatory environment and is endorsed by key opinion leaders in the EU. Previously the Company intended to await the results from the ongoing randomized, phase 3 OCEAN study before submitting an application for marketing authorization. Upon completion, the outcome from the OCEAN study comparing melflufen and pomalidomide in patients with RRMM, will be submitted to regulatory authorities to potentially expand the label of melflufen.

The HORIZON study demonstrates that melflufen in combination with dexamethasone has a potential to provide a therapeutic option for patients with RRMM that are hard to treat and have a poor prognosis, including patients with triple-class refractory myeloma and patients with extramedullary disease (EMD).

"Key opinion leaders and clinics across Europe have gained extensive experience of melflufen from our clinical development program in multiple myeloma. We share a mutual interest to enable early access to this rapidly growing patient population in desperate need of new treatment options", says Klaas Bakker, CMO of Oncopeptides.

According to the European Medicines Agency, medicines are eligible for conditional approval if they are aimed at treating or preventing seriously debilitating or life-threatening diseases. Conditional marketing authorizations may be granted if; the benefit-risk balance of the product is positive, comprehensive data can be provided, there is an unmet medical need, and the benefit to public health of making the product available outweighs the risks due to need for additional data.

The US Food and Drug Administration, FDA, has granted priority review to Oncopeptides´ New Drug Application of melflufen in combination with dexamethasone for treatment of patients with multiple myeloma. The FDA has set a target date for the review of the New Drug Application, to February 28, 2021.

On October 12, 2020 Kuur Therapeutics, a leader in the development of off-the-shelf CAR-NKT cell immunotherapies for the treatment of solid and hematological malignancies, reported the publication in Nature Medicine of interim findings from its ongoing phase 1 GINAKIT2 clinical trial collaboration with Baylor College of Medicine and Texas Children’s Hospital, in high risk relapsed refractory (R/R) patients with neuroblastoma, a form of childhood cancer (Press release, Kuur Therapeutics, OCT 12, 2020, View Source [SID1234568344]).

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The interim results demonstrated that expressing the CAR with interlukin-15 (IL-15), a natural protein that supports NKT survival, enhanced the tumor-fighting capabilities and in vivo persistence of autologous NKT cells. Two of three patients studied showed tumor reduction following CAR-NKT infusion: one classified as stable disease and the other as a partial response. Imaging revealed a dramatic reduction in the size and metabolic activity of bone metastases in the patient with the partial response. CAR-NKT cells demonstrated a favorable safety profile and localized to the site of the neuroblastoma tumors.

Kuur is the first company to test CAR-NKT cell therapy in patients. The company’s revolutionary platform engineers CARs on invariant NKT cells, a subset of T lymphocytes. NKT cells represent the next generation of CAR therapy, because this innovative approach harnesses the innate tumor-homing properties of NKT cells, a specialized type of lymphocyte that eliminates tumor-supportive macrophages, activates anti-tumor NK, dendritic and CD8 T cells, and does not induce graft versus host disease when used in an allogeneic setting.

"These results validate the biology of CAR-NKT cells in that they home to tumor and marrow, expand and have tumor killing properties. They also demonstrate safety and enhanced tumor homing capabilities, offering distinct advantages over other cell types for the treatment of solid and hematological tumors," said Kurt C. Gunter, MD, CMO of Kuur. "Using our novel engineering platform, we have manufactured CAR-NKT cells with high purity and added IL-15 to the CAR construct, which further increases in vivo persistence and anti-tumor activity. We look forward to continuing our research with the experts in cellular and gene therapy at Baylor as we aim to leverage the CAR-NKT cell approach to create more precise and effective therapies for cancer patients, including allogeneic therapies."

The results published were derived from the three heavily pre-treated, R/R metastatic neuroblastoma patients in dose level 1 (3×106 CAR-NKTs/m2) of the GINAKIT2 clinical study. These data were originally presented at the 23rd Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) in May 2020. The trial is currently enrolling at the fourth and highest dose level.

About KUR-501

KUR-501 is an autologous product in which natural killer T (NKT) cells are engineered with a chimeric antigen receptor (CAR) targeting GD2, which is expressed on almost all neuroblastoma tumors. KUR-501 is also designed to address key limitations of current CAR immune cell therapies by secreting the cytokine IL-15, which has been shown in nonclinical studies to increase the persistence of CAR-NKT cells and improve their efficacy within the immunosuppressive tumor microenvironment. KUR-501 is being tested in the phase 1 GINAKIT2 clinical study (NCT03294954) in patients with R/R high-risk neuroblastoma. The KUR-501 development program is also designed to provide autologous proof-of-concept for CAR-NKT cells in solid tumors using a validated target.

About the Licensing Agreement with Baylor College of Medicine

Kuur’s partnership with Baylor College of Medicine’s Center for Cell and Gene Therapy was first announced in March 2020 with the goal of advancing Kuur’s novel anti-cancer therapies via its innovative CAR-NKT platform. The platform was developed in the laboratory of Baylor principal investigator Dr. Leonid Metelitsa, an expert in the role of NKT cells in tumor immunity and a pioneer in applying this knowledge to NKT cell-based cancer immunotherapies. Kuur has an exclusive license to this platform and certain cell therapy candidates.

On October 12, 2020 Targovax ASA ("Targovax" or "the Company"; OSE: TRVX), a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, reported that the European Patent Office has granted European Patent no 3293201 (Press release, Targovax, OCT 12, 2020, View Source [SID1234568302]). The patent covers the use of ONCOS-102 in combination with checkpoint inhibitors.

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Torbjørn Furuseth, Chief Financial Officer of Targovax, said: "We are delighted that this European patent has been granted, further strengthening Targovax’s intellectual property portfolio covering the very important combination of ONCOS-102 and anti-PD1 checkpoint inhibitors. The oncology market is ever expanding, with the immuno-oncology segment expected to see the largest growth in the coming years. Securing this patent protects our innovative oncolytic immunotherapy platform and strengthens our market position."

In 2019 Targovax reported encouraging data from part 1 of a trial in PD-1 checkpoint refractory melanoma. This trial examines how ONCOS-102 reactivates the immune system of patients that have progressed on checkpoint inhibitor treatment. The aim is to trigger relevant T-cell production and infiltration into the tumor so that patients who have become refractory can benefit from retreatment with the checkpoint inhibitor. Data from part 2 of this trial is expected later in 2020.

Targovax’s lead product candidate, ONCOS-102, is a genetically modified oncolytic adenovirus, which has been engineered to selectively infect cancer cells and activate the immune system to fight the cancer. ONCOS-102 is currently being tested in mesothelioma, melanoma ovarian and colorectal cancers and has already shown promising clinical results both as monotherapy and in combination with chemotherapy, and checkpoint inhibitors.

On October 12, 2020 CURE Media Group, the industry-leading multimedia platform devoted to cancer updates and research that reaches over 1 million patients, reported that it has named the winners of its Third Annual Ovarian Cancer Heroes awards program (Press release, CURE Media Group, OCT 12, 2020, View Source [SID1234568345]). The virtual celebration will be held Friday, Oct. 16, 6-7:30 p.m. CDT, in conjunction with the National Ovarian Cancer Coalition Together in TEAL- No Boundaries.

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Keynote speaker Joan Lunden, award-winning journalist, bestselling author, patient advocate and breast cancer survivor, will join this year’s annual evening of gratitude and celebration honoring these three extraordinary individuals from across the globe who have gone above and beyond, making a difference in the lives of those affected by ovarian cancer.

The 2020 OC Heroes winners are the following:

Robin Cohen, B.S.N., RN, OCN, is the CEO and co-founder of the Sandy Rollman Ovarian Cancer Foundation in Wynnewood, Pennsylvania. She is a member of the Oncology Nursing Society, the Society of Gynecologic Nurse Oncologists and Cambridge Who’s Who. Cohen has been recognized as one of the 75 Greatest Living Philadelphians and is the 2016 recipient of the Cindy Melancon Spirit Award. She has served on the board of directors of the Ovarian Cancer National Alliance, is currently the vice president of the Board of the Ovarian Cancer Research Alliance and serves on the board of the World Ovarian Cancer Coalition. Cohen works on behalf of women with ovarian cancer every day so that they can live better and longer lives.
Deborah Zajchowski, Ph.D., is the scientific director of the Clearity Foundation in San Diego, California and oversees the foundation’s treatment decision support services and research efforts. She ensures that patients receive information about the most advanced treatment options for ovarian cancer — tailored to their specific tumor and clinical situation — through one-on-one consultations and regularly updated online resources. As a cancer biologist, Zajchowski has been involved in cancer research and drug/target discovery and development for more than 25 years. Zajchowski is a member of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) and the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and has published many research articles on cancer genomics, estrogen action and transcriptional control.
Andrea Herzberg is a 24-year survivor of late-stage ovarian cancer. She received her diagnosis at age 39. Born in Brooklyn, Herzberg graduated from the University at Albany (formerly known as State University of New York at Albany) in 1977. As a news reporter, she worked for the Troy, New York, Times Record and United Press International. Her second career was in community policing. As a rookie, she started out as a beat cop in New York City’s Chinatown. After 26 years in the New York City Police Department, she retired in 2011 with the rank of sergeant, supervisor of a detective squad, from the Special Victims Division. Now, as coordinator of SHARE’s cancer support toll-free ovarian helpline, Herzberg recruits and trains volunteers who are both compassionate listeners and passionate about helping callers find information, support and hope. Herzberg feels privileged to know these women who use their own experiences with a life-threatening illness to help others.
"Congratulations to these remarkable heroes who have dedicated their efforts to raising awareness, education and research in ovarian cancer," said Mike Hennessy Jr., president and CEO of MJH Life Sciences, parent company of CURE Media Group. "Seeing firsthand the compassionate care the medical staff provided to my mother during her ovarian cancer diagnosis, was incredible and has made a lasting impression. We are so grateful to be joined by Joan Lunden and look forward to honoring each hero with their family, friends and colleagues at the Ovarian Cancer Heroes virtual recognition ceremony."

As the longest running female host ever on early morning television, Lunden was the co-host of Good Morning America for nearly two decades. In 2014, Lunden was diagnosed with triple-negative breast cancer, which required chemotherapy, surgery and radiation. An eternal optimist, Lunden turned her diagnosis into a mission to educate and inspire others about prevention, treatment and survival. Throughout Lunden’s treatment, she blogged about her journey on her website and shared her battle and the transformative effect it has had on her life in her book "Had I Known." She has also sought ways to promote change and has successfully advocated for other survivors on Capitol Hill. As host of the PBS Series, ‘Second Opinion with Joan Lunden’ and the Washington Post Podcast, ‘Caring for Tomorrow’, Lunden continues to advocate for health, wellness, and actively communicates with Americans daily through both her social media and her website, JoanLunden.com.

"We are honored to be part of this event once again, and to recognize the remarkable efforts that are being made in the field of ovarian cancer, especially during these unprecedented times," said Mike Petroutsas, senior vice president of the US Oncology Business Unit at GSK. "At GSK, we share a similar mission of improving the lives of women with ovarian cancer, and are proud to offer resources that educate, empower and support this community. I am truly inspired knowing that with our collective efforts, we can help women and their loved ones find a way forward."