Jacalyn Rosenblatt, MD

Multiple myeloma is a type of cancer that affects plasma cells. This disease can lead to infections, kidney problems, and bone pain or fractures. There have been great improvements in the treatment of multiple myeloma in recent years. However, most people are still not cured by current therapy. Treatments that use the immune system have shown great promise. One important example is CAR T-cell therapy. CAR T cells are made by taking a patient’s T cells (a type of immune cell), and changing them so they can recognize and kill cancer cells. These cells are then given back into the patient by an intravenous infusion. CART cell therapy has resulted in dramatic improvements in outcomes for patients with multiple myeloma. Our group has studied a new combination approach to improve upon responses to CART cell therapy. We have developed a personalized cancer vaccines using a patient’s own cancer cells. To make the vaccine, a patients plasma cells are collected from the bone marrow and are combined with immune cells called dendritic cells, which help activate the immune system. In a national study, this vaccine was shown to be safe, could be made at centers across the country, and was shown to stimulate immune responses.  In this new study will test the vaccine in combination with CAR T-cell therapy. This DC/MM fusion vaccine has the potential to stimulate a broad immune response, preventing the development of resistance and can expand the CART cells to enhance their durability and effect.

Tannishtha Reya, PhD

Acute Myelogenous Leukemia (AML) is a fast-growing cancer of the blood and is the most common type in adults. Unfortunately, current treatments often don’t work well, and many patients get sick again or die. That’s why new and better treatments are needed. In our research, we looked at a protein that is found in large amounts on the outside of leukemia cells. Our earlier studies showed that this protein is needed for the cancer to grow. Because it’s on the outside of the cell, we can try to block it using special tools called antibodies. These antibodies attach to the protein and stop it from working. Here, we propose to develop an antibody that is able to target the protein and stop the cancer cells from growing. If we are successful, we plan to test the antibody in patients who are newly diagnosed or who haven’t gotten better with current treatments. This new antibody treatment could be a powerful new way to help people with AML live longer and healthier lives.

Jennifer McQuade, MD

Immunotherapy is a type of cancer treatment that helps the body’s immune system fight cancer. It has changed how we treat many cancers. But not all patients benefit from it. So, we need new ways to make this treatment work better. One area of interest is the gut microbiome. This is the group of trillions of bacteria that live in our gut. These bacteria can affect how the immune system works and how well immunotherapy works. Our research, and that of others, has shown that people who respond to immunotherapy have different gut bacteria than those who do not. Diet plays a big role in shaping the gut microbiome, as the bacteria in our gut eat what we eat. We have shown that diet is linked to how well people respond to immunotherapy. In mice, changing the diet changed both the gut bacteria and the response to treatment. Now, we are testing if diet changes can help patients who are starting immunotherapy. We want to see if we can improve their gut bacteria and boost their immune response through their diet. If this works, it could be a simple and low-cost way to help more people benefit from immunotherapy. We also found that a plant-based, high-fiber diet lowers certain bile acids in the body; these acids may weaken the patient’s immune response. In this study, we will test if these bile acids can be used as a marker of the extent to which the diet and treatment are working.

Kristy Brown, PhD

Women with excess body weight are more likely to get breast cancer than women with a healthy weight. The effect of excess body weight is especially harmful to women with a family history of breast cancer. Excess body weight can cause many harmful effects to cells. By limiting or reversing these changes, we may be able to prevent breast cancer. We think that exercise or weight loss can decrease the risk of breast cancer by reducing damage to cells. This is very important as it may provide options for women who decide not to get prevention surgery. In the future, we will apply what we have learned to a clinical trial.

Katerina Politi, PhD

In honor of Katie McDonald*

Lung cancer is the leading cause of cancer death worldwide and deeply affects many families. Twenty years ago, the discovery of mutations in the Epidermal Growth Factor Receptor (EGFR) gene and therapies that were effective for these tumors (targeted therapies) transformed the field and the lives of patients with this disease. This remarkable progress resulting from targeted therapies is countered by the fact that metastatic EGFR-driven lung cancer remains incurable due to the emergence of drug resistance. Therefore, there is an urgent need to improve treatment of EGFR-driven lung cancer so people live longer and ultimately cure the disease. Through our studies we have found new possible drug targets in this disease. In this proposal, we plan to understand whether these are new targets and how they work. We will also test drugs that have been developed against these targets in mouse and human models of EGFR-driven lung cancer. These studies will allow us to develop the foundation for designing a clinical trial for patients with EGFR-driven lung cancer with the goal of finding better ways of preventing and/or overcoming drug resistance and improving and extending the lives of people living with this disease.

Tullia Bruno, PhD

We aim to stop suffering and deaths from ovarian cancer. Therefore, we will explore how to improve the immune system’s ability to fight cancer. Cancer forms when normal cells change and grow wildly. The immune system can destroy abnormal cells. But cancer cells often evade immune system attacks. Ovarian cancer is a challenge. Only 10% of patients improve or survive with current treatments that help the immune system fight cancer. We study immune cells (B cells) and “neighborhoods” (tertiary lymphoid structures, or TLS) where these cells live. TLS can organize immune cells to fight cancer, and we investigate factors in ovarian cancer that impact TLS. We will test how immune cells (B cells) and non-immune cells (stromal cells) affect TLS creation and function. Our studies will show new ways to fight ovarian cancer. We will develop and lead new clinical trials. We will be poised to test a treatment for patients within five years that could change lives.

Rina Plattner, PhD

The number of melanoma cases in the United States continues to rise. When melanoma spreads to other organs, it is very deadly. Patients with this disease are usually first treated with medicines that help the immune system fight the cancer. This treatment works well for some people, but many can’t take the drugs because they have too many side-effects or simply do not work. For others, the medicines shrink the melanomas at first, but then they grow back. When immune medicines stop working, people with some kinds of melanomas can take other medicines(targeted drugs). However, targeted drugs do not work for a type of melanoma called NRAS mutant, which is very deadly and hard to treat. We found that a medicine used to treat leukemia may help targeted drugs work better for patients with this type of melanoma. In this proposal, we will learn how and why the leukemia medicine helps the targeted drugs work. We also will test our FDA-approved leukemia drug together with two different targeted drugs in mice. If the drugs work together to shrink the melanomas, then, in the future, we will test the treatment in patients by starting a clinical trial. Through this work, our goal is to give these patients more time to spend with their families, and eventually find a cure for this terrible disease.

Jennifer Rosenbluth, MD, PhD

A recent study showed that short-term, low-dose therapy can provide lasting protection from cancer. Yet only two drugs are approved for breast cancer prevention in the US. One reason is the lack of clear signs that show a risk-reduction therapy is working. One possible sign is background enhancement on breast MRI. A higher level means a higher risk of getting breast cancer. When a patient lowers their risk by taking tamoxifen, the background also goes down. For others, it does not. This shows that the therapy is not working. We studied breast tissue to understand the reason for this background. We found that those with high levels had either high estrogen or signs of inflammation. In our new study, we will use tissue pieces from patients starting tamoxifen. Our goal is to find a molecular signal that shows the drug is working. For those who do not respond, we will test drugs that target inflammation. Finally, we will see if different background signals point to estrogen or inflammation. These signals could be assessed in a clinical trial at UCSF to support a personalized cancer prevention strategy.

Xin Zhou, PhD

This project is about making a type of cancer treatments called antibody-drug conjugates, or ADCs. ADCs are protein-based therapies designed like guided missles. They carry strong cancer-fighting drugs and deliver them directly to cancer cells using antibodies. But in many cases, the drug doesn’t get inside the cancer cell well enough, so the treatment doesn’t work as well as it could. We are trying to solve this problem by using a special feature on the surface of cancer cells called an internalizing receptor. This is a protein that acts like a fast-moving doorway—it pulls things inside the cell quickly. By connecting the drug to an antibody that targets this fast moving receptor, we hope to get more of the medicine inside the cancer cell, where it can do its job. We are focusing on two hard-to-treat cancers: triple-negative breast cancer and some types of lung cancer. We will test our new treatment in the lab and in models of these cancers. We will also study large research databases to learn which types of tumors might respond best. This research matters because many people with cancer still don’t have good treatment options. If this new approach works, it could lead to more effective and more targeted cancer treatments. It may help more patients benefit from ADCs, especially those with cancers that don’t respond well to current therapies.

Andrew Koh, MD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Immune checkpoint inhibitor therapy (ICT) is a form of cancer therapy that boosts the immune system to kill cancer cells.  ICT can help cure some adult cancers but has not been effective in children with cancer. This proposal explores whether a combination of standard cancer therapy and ICT is both safe and effective in children with solid tumors in a clinical trial.  First, we will test tumor, blood, and stool samples collected from patients in this clinical trial.  We will attempt to learn what factors determine whether a patient will respond to this combination therapy or not respond. Second, we will use mouse cancer models to test different combinations of standard cancer therapy and ICT to see which combinations work the best.   This work will help us understand if combining standard cancer treatments with ICT is both safe and effective in children with solid tumors.

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