cancer immunotherapy Archives - Sanford Burnham Prebys

Tag: cancer immunotherapy

Institute News

Meet immunologist Jennifer Hope

AuthorMonica May
Date

February 12, 2021

Jennifer Hope photo in lab

Hope’s research aims to help cancer immunotherapy work for more people

It’s not an overstatement to say that immunotherapy—an approach that uses our own immune system to kill a tumor—has revolutionized the treatment of cancer. Doctors continue to report incredible results, including tough-to-treat tumors seemingly melting away. However, the treatment doesn’t work for everyone, and even if it does work initially, it often stops working as time goes on.  

Jennifer Hope, PhD, a postdoctoral researcher in the Bradley lab at Sanford Burnham Prebys, is working to find ways to make cancer immunotherapy work for more people. We caught up with her as she prepared to take the virtual stage at the Diversity and Science Lecture Series at UC San Diego (DASL) to learn more about what she wishes people knew about science and whom she admires.

Did you always know you wanted to be a scientist?
I always had an interest in science, but at first I wanted to go a totally different route. I was an athlete in high school and college—I played tennis—and really wanted to go into sports medicine. Then I had my first real experience being in a lab in college, and I was hooked. I liked how hands-on it was and how I could keep asking questions. As my family knows, I’ve always been one to ask a lot of questions and always ask why. I found that being in the lab that was my opportunity to keep coming up with new questions, and finding answers that will impact people’s lives.

What do you research, and what is your greatest hope for your work?
I’m trying to understand why the immune system—specifically, T cells—seems to turn a “blind eye” to tumors, which it doesn’t do to other foreign invaders like viruses. My ultimate hope is that we use this information to create better cancer immunotherapies, particularly for skin cancer, which is still really deadly.

What do you wish people knew about science?
That it can be a lot of fun! Most people have this perception of science as being very boring. You see X and you do Y. That part can be true. But there’s a lot of opportunity for creativity and to come up with different ways to ask the same question. Some of the best scientists are incredibly creative people.

How would your coworkers describe you?
Motivated and always willing to try new things.

When you aren’t working, where can you be found?
Reading a book. My family started a book club to stay connected during the pandemic. We just read The Food Explorer by Daniel Evan Stone, which was fascinating. It’s about a botanist who is responsible for transforming what food looked like in the U.S. at the turn of the century. I don’t want to give too much away, but it’s because of him that we have cherry blossoms in Washington D.C., and regulations on importing seeds.

Whom do you admire, and why?
My parents. It sounds cliché, but it’s true. They have always been the biggest supporters of my dreams, whether career or personal.

One example that pops into my head is when I was getting my PhD, and my PI moved from Philadelphia to the Netherlands. I had the opportunity to move, too, if I wished. This was obviously a huge step, and I called my parents to talk it through. Immediately, the conversation was about how this would benefit me—the risks and the advantages—and they said they would support me if I wanted to go or not. That meant, and means, the world to me. Ultimately, I did go, and it was an incredible opportunity that I don’t regret at all.

What do you wish people knew about Sanford Burnham Prebys?
That everyone is willing to help each other. You don’t see that everywhere. It is proof that you can do science at an exceptional level without competing with each other.

Institute News

5 things to know about immunotherapy and breast cancer

AuthorSusan Gammon
Date

September 30, 2019

Svasti Haricharan, PhD, Sanford Burnham Prebys

If you follow news about medical breakthroughs, you have undoubtedly heard about immunotherapy to treat cancer.

This form of therapy is designed to prime the body’s own immune system to fight the disease head-on. For some cancers, such as melanoma and lung cancer, immunotherapy has helped patients who once had only a life expectancy of months now live for years. But does it work for other cancers?

We sat down with Svasti Haricharan, PhD, assistant professor at Sanford Burnham Prebys and recipient of a Susan G. Komen Career Catalyst Award to discuss where we are with immunotherapy and breast cancer. Here are five things she wants us to know.
 

  1. As scientists, our job is to understand the biology of why immunotherapy works for some cancers but not others. Our goal is to develop approaches to expand the benefits of immunotherapy to as many patients as possible. With breast cancer, we are still in the early days, but there has been some success. Earlier this year a type of immunotherapy called an “immune checkpoint inhibitor” was approved to treat certain types of metastatic breast cancer. But immunotherapy doesn’t work—yet—for all breast cancers.
     
  2. No two breast cancers are alike. Even though two women with breast cancer may have the same size tumor, the individual characteristics of the tumor—the receptors, the genetics, even the way the tumor cells gather fuel to grow, can differ. Just as importantly, the way each woman’s body reacts to the growing cancer is predicated by her immune history: her exposure to immunological challenges, the strength of the immune response her body is capable of mounting, and how long she can sustain an immune response. These factors strongly influence the likelihood that a patient will respond to a specific therapy. The more we drill down on breast tumors, and the tricks they use to evade the immune system, the closer we get to outsmarting them.
     
  3. Today, immunotherapy seems to work best for triple negative breast cancer. Triple negative means three types of receptors—estrogen receptor, progesterone receptor and HER2—are not expressed on the cancer cells. Cancers that express these receptors are easier to treat because these receptors can be targeted directly. We believe part of the reason why immunotherapy is effective for triple negative breast cancer is because these cells can grow rapidly and produce more neoantigens—altered tumor proteins that have not previously been recognized by the immune system. So, these tumors may already have immune cells infiltrating the tumor, and when unleashed via immunotherapy, they can readily attack the cancer. 
     
  4. Immunotherapy—at least the immune checkpoint agents that are used today—target a protein called PD-1 found on T cells, which are the immune cells that roam the body looking for disease. PD-L1 is another protein found on some normal and some cancer cells. When PD-1 attaches to PD-L1, T cells are queued to leave the cell alone and not attack it. We believe cancer cells use PD-L1 to protect themselves from the immune system, and that cancers with large amounts of PD-L1 are the most likely to respond to checkpoint inhibitors. It’s possible that testing breast tumors for PD-L1 levels will help identify more women likely to benefit from these drugs. 
     
  5. Collaboration is key. Although we like to think of scientists as having “Eureka” moments, the reality is that much of the progress we make is incremental. We painstakingly plan, control and execute experiments—gathering and analyzing data to open new avenues that can be tested in the clinic. Working alongside professionals who are responsible for patient outcomes is an important part of the research spectrum. Their input provides direction for our goal of achieving cures—and a means to evaluate if what started in the lab will work in the clinic. There are nearly 300 clinical trials currently ongoing that are testing immunotherapeutic approaches for breast cancer. The information we gather from these trials helps guide the future of what we do next in the laboratory. Advances will be made, and progress is on the horizon.
     
Institute News

SBP President’s Lecture highlights new approach to cancer immunotherapy

AuthorLindsay Ward-Kavanagh
Date

February 27, 2017

T cells (pseudo colored pink) interacting with dendritic cells (pseudo colored green)

One of the most promising new approaches to treating cancer is immunotherapy—redirecting the immune system to detect and destroy tumor cells. That’s the topic of this year’s President’s Lecture by Andrew Weinberg, PhD, chief of the Laboratory of Basic Immunology at Providence Portland Medical Center, on 28 February 2017.

His research is related to the work of scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) working to harness the power of killer T cells that can recognize and eliminate cancerous cells.

The laboratory of Linda Bradley, PhD, professor at SBP, recently published a paper identifying PSGL-1, a protein that limits T cell responses to viruses, as a new target for checkpoint inhibition, an approach akin to taking the “brakes” off the immune system. They showed that T cells in mice that could not make PSGL-1 delayed tumor growth, suggesting that blocking PSGL-1’s function would help T cells fight tumors.  

Conversely, Carl Ware, PhD, professor and director of the Infectious and Inflammatory Diseases Center, is developing an immunotherapy strategy that’s the equivalent of “hitting the gas” to expand anti-tumor responses. Their project exploits the protein LIGHT, which turns on multiple pathways required for strong T cell responses. Ware’s current goal is to create an optimized mutant form of LIGHT with the strongest ability to drive anti-tumor immunity.

Weinberg uses a similar “hitting the gas” approach to immunotherapy, targeting the T cell co-stimulator OX40 with a drug now in clinical trials.

“Immunotherapy drugs currently approved to treat cancer block the negative signals that minimize T cell activity,” explains Ware. “Weinberg’s  work is different because the drug, called an OX40 agonist, boosts positive signals to T cells. His work has really led to this new approach of targeting immune molecules to enhance T cell function.”

Weinberg’s pioneering research revealed how OX40 identifies functional T cells in cancer and autoimmune disease patients. He confirmed the anti-tumor potential of OX40 in mice when antibodies that stimulated OX40 activity expanded the T cell population within tumors, and drove tumor regression. The identification of this anti-tumor potential ultimately led to the creation of the company AgonOx, which has commercially developed OX40 agonists in collaboration with AstraZeneca.

As clinical trials with OX40 agonists continue, Weinberg still recognizes the value of basic research. He says, “Understanding immunology in its most basic form can help us understand the principles and mechanisms involved with how these drugs work. If we understand how they work we can make them better, or choose combinations that will improve their efficacy.”

Institute News

Genetic drivers of immune response to cancer discovered through ‘big data’ analysis

AuthorJessica Moore
Date

July 18, 2016

big data

Scientists at the Sanford Burnham Prebys Medical Discovery Institute (SBP) have identified over 100 new genetic regions that affect the immune response to cancer. The findings, published in Cancer Immunology Research, could inform the development of future immunotherapies—treatments that enhance the immune system’s ability to kill tumors.

“By analyzing a large public genomic database, we found 122 potential immune response drivers—genetic regions in which mutations correlate with the presence or absence of immune cells infiltrating the tumors,” said lead author Eduard Porta-Pardo, PhD, a postdoctoral fellow at SBP. “While several of these correspond to proteins with known roles in immune response, many others offer new directions for cancer immunology research, which could point to new targets for immunotherapy.”

Immunotherapy has been heralded as a turning point in cancer because it can treat even advanced cases that have spread to other organs. Several drugs in this class are now widely used and often lead to remarkable success, eradicating or dramatically shrinking tumors and preventing recurrence.

Most current immunotherapies rely on a similar strategy—releasing the brakes on the immune system. These treatments are powerful if the tumor is recognized by the immune system as a threat and allows immune cell infiltration, but some cancers remain undercover or block immune cell entry into the tumor in as yet unknown ways.

“To develop immunotherapies that are relevant to a wide range of cancers, we need to know a lot more about how the immune system interacts with tumors,” said Adam Godzik, PhD, professor and director of the Bioinformatics and Structural Biology Program and senior author of the study. “Our study provides many new leads for this endeavor.”

“We are exploring cancer mutations at fine resolution by accounting for the fact that mutations can affect the encoded protein in different ways depending on where the resulting change is located,” commented Porta-Pardo. “Our algorithm, domainXplorer, identifies correlations between a phenotype, in this case the amount of immune cells in the tumor, and mutations in individual protein domains—parts of a protein with distinct functions.

“This work emphasizes the value of open data,” Godzik added. “Because we could access genomic data from over 5,000 tumor samples from The Cancer Genome Atlas (TCGA), we could jump straight to analysis without having to set up a big collaborative network to gather and sequence so many samples.”

“Our plan for the next phase of this research is to use this algorithm to search for genetic regions correlating with the levels of specific immune cell types within the tumor, which will reveal further details of cancer immunology.”

 

Institute News

Symposium brings leaders in tumor immunology to SBP

Authorjmoore
Date

March 21, 2016

Header image

SBP’s La Jolla campus recently hosted a one-day conference on Cancer Immunology and the Tumor Microenvironment, one of the hottest topics in cancer research. The symposium on March 17 attracted approximately 160 attendees from across the La Jolla biomedical research mesa.

The symposium was organized by Carl Ware, PhD and Robert Rickert, PhD, directors of the Inflammatory and Infectious Disease Center and the Tumor Microenvironment and Cancer Immunology Program, respectively. They planned a scientific agenda that covered diverse aspects of research on harnessing the immune system to treat cancer, from improving current immunotherapies to identifying new immunological targets. Talks were given by prestigious scientists including:

Two SBP researchers also presented. Linda Bradley, PhD, professor in the Immunity and Pathogenesis Program, discussed her work on the immune cell surface protein PSGL-1, showing that it regulates PD-1, a so-called “immune checkpoint.” PD-1 is found on T cells and normally acts as on “off switch” to keep the immune system from attacking cells in the body. PD-1 regulators are a new approach to treating cancer that work by unleashing cytotoxic T cells to kill cancer cells.

 

Adam Godzik, PhD, professor and director of the Bioinformatics and Structural Biology Program, spoke about using bioinformatic analyses to search for new cancer drivers related to the immune response. Cancer drivers are genes that, when altered, are responsible for cancer progression. Combining cancer mutation and protein structure databases, his team has identified many genes involved in immune recognition of tumors.