PSCA-CAR-T Cells(Guangdong Zhaotai InVivo Biomedicine)

Trial results published today in Nature Medicine A phase 1b trial using the same CAR T cell therapy has opened LOS ANGELES--(BUSINESS WIRE)-- Treating prostate cancer with immunotherapy is currently difficult to do. But preliminary results from a first in-human phase 1 trial using a chimeric antigen receptor (CAR) T cell therapy developed by researchers from City of Hope®, one of the largest cancer research and treatment organizations in the United States, showed that patients with advanced prostate cancer had minimal side effects with the cellular immunotherapy and had promising therapeutic activity, according to a study published today in Nature Medicine. This press release features multimedia. View the full release here: Saul Priceman, Ph.D., City of Hope associate professor, Department of Hematology & Hematopoietic Cell Transplantation, and Tanya Dorff, M.D., City of Hope section chief, Genitourinary Disease Program, and their teams worked together on the phase 1 clinical trial using a City of Hope-developed CAR T cell therapy for prostate cancer. (Photo: Business Wire) The trial treated 14 prostate stem cell antigen (PSCA)-positive patients who had metastatic castration resistant prostate cancer (mCRPC), which had spread beyond the prostate and no longer responded to hormone treatment, using CAR T cell therapy. More than 34,000 men with this type of prostate cancer die each year in the United States. Saul Priceman, Ph.D., City of Hope associate professor, Department of Hematology & Hematopoietic Cell Transplantation, and team developed CAR T cells that target prostate stem cell antigen (PSCA) found to be highly expressed in prostate cancer. The treatment took a patient’s immune cells – known as T cells – from the bloodstream, and reprogrammed the cells in a laboratory with a CAR to recognize and attack the PSCA protein on the surface of cancer cells. CAR T cells were then infused back into the patient’s system to destroy cancer cells. “Prostate cancer has been called an immune desert — the tumor microenvironment is difficult to treat with immunotherapies because you don’t get a lot of T cells inside the tumor,” said Tanya Dorff, M.D., City of Hope section chief, Genitourinary Disease Program, and professor, Department of Medical Oncology & Therapeutics Research. “It takes something really powerful to overcome that. Our study showed that City of Hope’s CAR T cell therapy for prostate cancer could be a step closer to doing that.” “Our trial’s preliminary major finding is that PSCA-directed CAR T cells may be effective against mCRPC,” Priceman added. “This opens up the opportunity to continue to develop this type of cellular immunotherapy for these patients, who currently have no other effective treatment options.” The trial’s goals were to examine the therapy’s safety and dose-limiting toxicities, or side effects that limit the amount of treatment that can be administered, as well as preliminary data on the treatment’s efficacy in patients. The study’s findings were: Patients received a single infusion of 100 million CAR T cells without prior lymphodepletion chemotherapy, which is used routinely in blood cancers to improve the efficacy of CAR T cell treatment. Since this was a first-in-human CAR T cell trial, it was important to assess the safety of CAR T cells alone in patients. At that same CAR T cell dose and with lymphodepletion, there was a side effect of dose-limiting toxicity of cystitis, or irritation of the bladder. Dorff explained that PSCA is also found in the bladder so the CAR T cells most likely attacked the bladder cells, causing inflammation. Researchers then added a new cohort to the study using reduced lymphodepletion, which mitigated this toxicity. Four out of 14 patients had declines in their PSA levels, which is a serum marker of disease progression in people with prostate cancer, including one patient with a significant decline. Imaging showed therapeutic responses in a subset of treated patients. Five out of 14 patients had mild or moderate cytokine release syndrome, which can be caused by a large, rapid release of cytokines into the blood from immune cells and is a common side effect after CAR T cell therapy. CRS was a treatable side effect. CAR T cells did not persist at high levels beyond the 28-day monitoring period, which limits the therapy’s effectiveness. This presented a common challenge in the solid tumor CAR T cell field that researchers plan to address in a follow-up City of Hope trial using the therapy that is now open for enrollment. One patient who had received several prior therapies responded well to the CAR T cell therapy. His PSA level decreased by 95% and cancer in his bones and soft tissue also declined. He experienced this positive response for approximately eight months. “The patient’s results were very encouraging, and we are deeply grateful for his participation in our study as well as other patients and their families,” Dorff said. “We want to continue with this therapy and increase the amount of CAR T cells, and continue to carefully monitor for any health problems, as we think this can improve the therapy’s effectiveness.” The phase 1b trial using the PSCA-CAR T cell therapy in combination with radiation to enhance anti-tumor activity aims to enroll up to 24 patients. City of Hope, a recognized leader in CAR T cell therapies, has treated nearly 1,500 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 about 70 ongoing CAR T clinical trials, which include 13 different solid tumor types. The trials use City of Hope-developed therapies and industry-sponsored products. A recent study published in Nature Medicine featured City of Hope’s CAR T cell therapy for brain tumors. City of Hope manufactured the CAR T cells in its own facility, the Cell Therapy Production Center on its Los Angeles campus. The Prostate Cancer Foundation helped fund the trial. About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn. View source version on businesswire.com: Contacts Letisia Marquez 626-476-7593 lemarquez@coh.org Source: City of Hope Smart Multimedia Gallery Photo Saul Priceman, Ph.D., City of Hope associate professor, Department of Hematology & Hematopoietic Cell Transplantation, and Tanya Dorff, M.D., City of Hope section chief, Genitourinary Disease Program, and their teams worked together on the phase 1 clinical trial using a City of Hope-developed CAR T cell therapy for prostate cancer. (Photo: Business Wire) Logo View this news release and multimedia online at:

Research on a heart medication for childhood cancer survivors and new immunotherapies for blood and solid tumors will be presented. LOS ANGELES, May 26, 2023 /PRNewswire/ -- City of Hope, one of the largest cancer research and treatment organizations in the United States, today announced it would present research on promising treatments for blood, prostate and other cancers, as well as studies on germline testing for hereditary cancers and on reducing heart disease in childhood cancer survivors, at the 2023 American Society of Clinical Oncology's (ASCO) annual conference from June 2 to 6 in Chicago. Continue Reading More than 40,000 oncology professionals and others will attend the conference, or join virtually, to learn about the latest scientific research on cancer treatment, detection and prevention. City of Hope researchers present new treatments for blood, prostate and other cancers at 2023 ASCO conference Tweet this "This year's ASCO Annual Meeting highlights the exceptional work City of Hope doctors and scientists are leading with the hope of finding better treatments against a wide range of cancers," said Steven T. Rosen, M.D., City of Hope provost and chief scientific officer, Irell & Manella Cancer Center Director's Distinguished Chair. "Whether it's working on our own immunotherapy trials for solid tumors, or partnering with companies to find novel medicines, City of Hope is committed to transforming cancer care for our patients and beyond." City of Hope doctors and scientists will present oral and poster presentations on these and other abstracts: Blood pressure medication shows promise in lowering heart failure risk for childhood cancer survivors For people who were treated with anthracyclines — a class of chemotherapy drugs — for childhood cancers, heart failure can be a devastating side effect that develops later in life. To date, there have been no effective therapies to prevent heart failure in long-term childhood cancer survivors who have been treated with anthracyclines. Now, Saro Armenian, D.O., M.P.H., City of Hope's Barron Hilton Chair in Pediatrics, The Norman and Sadie Lee Foundation Professor in Pediatrics and director of the Division of Outcomes Research/Intervention, has led a Phase 2b clinical trial examining the effectiveness of a low-dose blood pressure medication called carvedilol to improve heart health in these survivors. The trial was double-blinded, meaning participants and doctors don't know which therapy is received until the trial is over, creating less bias, and placebo-controlled, which refers to a group of participants receiving a treatment that has no active properties. The trial was conducted at 30 sites and enrolled 182 participants to either receive low-dose carvedilol (12.5 mg/day) or a placebo. Armenian and his team found that carvedilol was shown to be safe and effective in reversing early signs of heart injury during the two-year study period. Compared to the placebo arm, participants who took carvedilol had significantly better left ventricular chamber size and left ventricular end-systolic wall stress — two measurements of heart health — at two years. "There are an estimated 500,000 long-term survivors of childhood cancer in U.S. alone and more than 40% will have been treated with anthracycline-based chemotherapies," said Armenian, who will give an oral presentation of the trial's outcomes on Monday, June 5, at 9:12 a.m. CDT. "Our study is one of the first to demonstrate the safety and efficacy of a readily available heart failure prevention strategy in long-term survivors, setting the stage for optimizing cardiovascular outcomes in this growing population of survivors who will live for decades after their initial diagnosis." Follow-up of participants is ongoing, which may inform the efficacy of the intervention beyond the two-year period. The team also has several research collaborations examining optimal strategies for remote patient monitoring for heart health in cancer survivors, which would allow real-time intervention prior to onset of irreversible cardiovascular injury. "Remote monitoring options could bridge the gap in the community setting for at-risk patients by allowing point-of-care cardiac assessments by primary care providers to help track their heart health, or by facilitating home-based surveillance by specialized survivorship centers," Armenian said. New treatment for relapsed or refractory leukemias performs well in first clinical trial For patients with blood cancers that have returned or are treatment-resistant, the existing therapy options are few. In an effort to expand treatment choices, Anthony S. Stein, M.D., associate director of City of Hope's Gehr Family Center for Leukemia Research and professor with the Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, and a team of researchers are testing a new approach. Early results from the first-in-human study of SAR443579 (SAR'579) in relapsed or refractory acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia, or high-risk myelodysplasia have revealed positive results. When activated, natural killer (NK) cells have innate cell killing function. SAR'579 is a trifunctional anti-CD123 NK cell engager which targets NK cells through CD16 and NKp46 and the tumor antigen CD123 on the AML cell. This co-engagement of the NK cells leads to an optimal activation resulting in tumor cell death. In an oral presentation titled "A first-in-human study of CD123 NK cell engager SAR443579 in relapsed or refractory acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or high-risk myelodysplasia," being presented on Friday, June 2, at 2:24 p.m. CDT, Stein will outline findings from 23 AML patients in a Phase 1/2 clinical trial who received SAR'579, under development by Sanofi, to evaluate the treatment for safety, efficacy, and anti-leukemic activity. Patients received a median of two cycles for a median duration of seven weeks with escalating doses. The most common adverse events were infusion-related reactions and nausea. "We found that SAR'579 was well-tolerated in heavily pretreated patients with refractory AML," Stein said. "In addition, we observed clinical benefits in the patients. Thirteen percent of all patients achieved a complete remission and 37.5 percent achieved a complete remission at the maximum highest dose of 1,000 micrograms per kilogram, once a week. These are encouraging findings for patients with AML." The clinical trial is still open and continues to accrue patients. Stein and his team are working to define SAR'579's optimal dose with the best safety and highest response profile. Benefits of brexu-cel treatment for relapsed or refractory mantle cell lymphoma hold up in large, real-world study Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T cell therapy and a Kite product. CAR T cell therapies use the body's own cells, known as T cells, from the immune system to fight cancer. Brexu-cel was first approved by the U.S. Food and Drug Administration in 2020 for relapsed or refractory (R/R) mantle cell lymphoma (MCL). Accelerated approval was granted based on a single-arm Phase 2 clinical trial called ZUMA-2. Now, an analysis led by Swetha Kambhampati, M.D., City of Hope assistant professor in the Division of Lymphoma, has shown the treatment to work well outside of the clinical trial. Kambhampati and a team of researchers evaluated follow-up, updated data from 380 patients who participated in the ZUMA-2 trial and were also registered in the Center for International Blood and Marrow Transplant Research observational database. They found that at a median follow-up of 12 months, the objective response rate, or cancer diminishing, was 90%, and the complete response rate, which refers to the disappearance of all signs of cancer, was 78% with a median duration of response of 21.7 months. These results were comparable to those seen in the ZUMA-2 trial. The team found that complete response rates were higher in patients who received brexu-cel in earlier lines of therapy, suggesting that treating R/R MCL patients with brexu-cel sooner may be beneficial. Kambhampati and others also examined outcomes based on prior treatment types and found them to be largely consistent in MCL patients who had received bruton tyrosine kinase inhibitors, a therapy that stops B cell growth to treat lymphoma, bendamustine (a type of chemotherapy), or autologous stem cell transplant therapy before taking brexu-cel. "Our results show that brexu-cel has demonstrated efficacy and safety in the real-world setting in R/R MCL, regardless of prior therapy and it has improved efficacy when used in the earlier lines of therapy," said Kambhampati, who will give an oral presentation on the study on Tuesday, June 6, at 11:57 a.m. CDT. "But, it will be important to evaluate the durability of responses with brexu-cel in R/R MCL further with longer follow-up." CAR T cell therapy tested in the treatment of metastatic castration-resistant prostate cancer patients Chimeric antigen receptor (CAR)-engineered T cell therapies represent a recent and huge advance in cancer care for blood cancers and some brain tumors. Researchers are now looking to apply the approach to more solid tumors, which represent roughly 90% of all adult cancers. CAR T therapies work by boosting the body's own immune system to fight disease. Saul Priceman, Ph.D., associate professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation and associate director of Translational Sciences & Technologies in the T Cell Therapeutics Research Laboratory, and Tanya Dorff, M.D., City of Hope's section chief, Genitourinary Disease Program, have been working to develop CAR T cell therapy for advanced prostate cancer. Dorff will share results from a Phase 1 clinical trial using CAR T in metastatic, prostate stem cell antigen (PSCA)-positive, castration-resistant prostate cancer patients during a poster discussion on Saturday, June 3, starting at 1:15 p.m. CDT. (Metastatic refers to a cancer that has spread and castration-resistant refers to prostate cancer that keeps growing despite little to no testosterone, which is what usually causes prostate cancer to grow.) Using a CAR T cell developed at City of Hope, Priceman, Dorff, and a team of researchers recruited 14 patients with PSCA-positive prostate cancer. PSCA is highly expressed in most prostate cancers and targeting PSCA with CAR T cell therapy has been previously shown to be potentially effective and feasible. The team found that the PSCA-CAR T cell therapy had anti-cancer effects in these patients and more so in patients who had also received lymphodepletion (LD) chemotherapy. They also found that a lower dose of LD chemotherapy lessened the toxicity, or harmful effects, of the treatment without clear negative impact on CAR T expansion. "More work needs to be done to optimize the use of CAR T cell therapy in prostate cancer since we are seeing occasional very deep responses, but not as many of them, or with as much durability, as we would like," Dorff said. "But we remain enthusiastic about the potential of this treatment. This study has pushed cellular immunotherapy one step closer to being a treatment option for advanced prostate cancer." To further test the approach, the team will open a Phase 1b clinical trial with a new dosing strategy soon, which they believe will achieve greater efficacy with lower toxicity. Universal germline testing could help identify people with hereditary breast-ovarian cancer syndrome to improve cancer control Many people with hereditary breast-ovarian cancer syndrome (HBOC) and Lynch syndrome — caused by mutations in the genes, such as BRCA1, BRCA2, ATM, PALB2, and Lynch syndrome associated-genes — are unaware of their risk to develop cancer. While screening efforts catch about half of the people carrying these mutations, a better approach is needed. City of Hope's Implementing Next-generation Sequencing for Precision Intervention and Risk Evaluation (INSPIRE) study, led by Stephen Gruber, M.D., Ph.D., M.P.H., the Eva and Ming Hsieh Family Director's Chair of the Center for Precision Medicine, Stanley Hamilton, M.D., professor and chair of the Department of Pathology, and Stacy W. Gray, M.D., professor and chief of the Division of Clinical Cancer Genomics and deputy director of the Center for Precision Medicine, hopes to be just that. The research project makes germline genetic testing available without charge to every participating City of Hope patient. "Every mutation that is known to be associated with elevated cancer risk is actionable at some level," said Gray, who will be presenting data at ASCO from the INSPIRE study. "It could mean increased screenings to catch cancer at its earliest, most treatable stages, or risk-reducing surgery or new medications." In a poster session on Saturday, June 3, from 1:15 to 4:15 p.m. CDT, Gray will outline recent findings from an informatics study aimed at determining whether genetic testing, through outreach like INSPIRE, leads to increased intervention for people carrying the BRCA mutation. By querying codified data, which refers to grouping data in meaningful categories, in City of Hope's electronic data warehouse before and after germline testing, Gray and her study collaborators found that out of 217 patients whose testing revealed a known or likely BRCA mutation, 83% had procedures, imaging and/or therapy potentially related to the BRCA mutation. "This suggests that universal genetic testing identifies patients who have inherited cancer risk who previously did not know their risk. Moreover, our study will evaluate whether individuals with BRCA and other actionable germline findings receive higher levels of relevant health care," Gray said. "However, this initial informatics approach is limited because key information on prior germline testing and motivations for surgery, such as whether a patient received a mastectomy as part of a treatment plan or chose one as a preventive measure, are not adequately captured in codified data." She says that codified electronic health record queries will need to be augmented by text mining and/or manual chart review to fully capture care and assess the clinical utility of system-wide genetic care delivery interventions. Given the promising findings of this initial work, Gray and the team are now evaluating care for the more than 17,000 patients who have enrolled in the INSPIRE study. About City of Hope City of Hope's mission is to deliver the cures of tomorrow to the people who need them today. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope's growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and treatment facilities in Atlanta, Chicago and Phoenix. City of Hope's affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, Twitter, YouTube, Instagram and LinkedIn. SOURCE City Of Hope