Researchers detail new findings at 2019 AACR meeting

Leading the path into the next stage of immunotherapy, City of Hope is enrolling patients in an autologous T cell clinical trial that aims to re-engineer and use a patient’s own immune T cells to attack solid tumors in the body. Enhanced T cell therapy has been successful in treating hematologic (blood) cancers and is in early development for solid tumors.

 

The randomized 1a/2b study will investigate the safety and efficacy of enhancing a patient’s own T cells with NY-ESO-1/LAGE-1a antigens so that his or her immune system will better attack advanced nonsmall cell lung cancer. The therapy, of course, can be used only in people whose tumors express the NY-ESO-1 and/or LAGE-1a receptors.

 

Today’s standard of care for advanced nonsmall cell lung cancer leads to long-term benefits for about 10 percent of patients, said Karen Reckamp, M.D., M.S., co-director of the Lung Cancer and Thoracic Oncology Program at City of Hope and principal investigator of the ongoing clinical trial. The majority of patients with this disease have few treatment options. “T cell therapy is a high priority for City of Hope,” Reckamp said. “We hope to move enhanced T cell therapy forward in solid tumors, especially in lung cancers.”

 

In the ongoing clinical trial, the patient’s engineered T cells, called GSK3377794, will be used alone and in combination with pembrolizumab, a monocolonal antibody that blocks PD-1/PD-L1 interaction and increases the antitumor function of T cells. The synergistic treatment potentially can help certain patients with Stage 3 or Stage 4 nonsmall cell lung cancer — people who have tried other treatments but have not been able to find their way back to health.

 

The study is a part of the California Institute for Regenerative Medicine-sponsored City of Hope Alpha Stem Cell Clinic. It is supported by GlaxoSmithKline and is a collaboration with Merck & Co. Inc.

City of Hope and its affiliate Translational Genomics Research Institute (TGen) is collaborating with others to create the future of oncologic radiology — what City of Hope’s Syed Rahmanuddin, M.B.B.S., calls “the mammogram of pancreatic cancers.” His team is using top-of-the-line technology to create artificial intelligence algorithms that compile a detailed 3D image of pancreatic cancer. The purpose is to enable physicians to identify the volume of blood flow (perfusion kinetics) of tumors and learn how effective a treatment is, facilitating adjustments to regimens to allow for improved targeted cancer therapy. Right now, the standard of care is flat, black-and-white multiphase computed tomography (CT) imaging. “Our new, patient-centered 3D imaging approach is like the transition from thinking the world is flat to understanding that the world is a globe: It opens up a whole world of possibility,” Rahmanuddin said. “Our pilot study suggests that change in 3D volume and perfusion (blood flow) are important imaging markers that correlate with tumor progression, regression and aggression, which could be very helpful for the early detection of pancreatic cancer.”

 

Daniel Von Hoff, M.D., physician-in-chief and distinguished professor of TGen, and Ronald Korn, M.D., Ph.D., of Imaging Endpoints, were key contributors to this research.

A molecule found on the skin of citrus fruits appears to inhibit the growth of breast cancer tumors in a mouse model. Compared to control mice with xenografted breast cancer cells, those who received 2’-Hydroxyflavanone (2HF) experienced reduced viability and proliferation of breast cancer cells. In addition, 2HF inhibited the expression of RLIP, a protein that is overexpressed in breast cancer cells. “While more research is needed to see if what we found in our mouse models can be translated to human subjects, it is important to note that natural compounds extracted from, say, orange peels is not toxic and has been shown to be beneficial, including lowering glucose triglycerides and cholesterol levels,” said Sharad Singhal, Ph.D., lead author of the study and research professor in medical oncology at City of Hope. “In the distant future, it’s possible that 2HF supplements can be taken by breast cancer patients to enhance the effectiveness of medical treatment.”

 

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