Cancer

Gladstone scientists are using CRISPR genome editing technology to better understand how immune cells can be trained to fight cancer. Alex Marson’s group is testing thousands of genes in human T cells to find the ones that make these cells stronger and more effective at killing tumor cells.

By studying how immune cells behave at a single-cell level, the scientists can see how they change inside tumors and during immunotherapy. These insights are then used to design new genetic programs that can rewire immune cells and improve cancer-fighting treatments, helping guide the development of future therapies.

Gladstone scientists are uncovering ways to turn cancer’s own biology against itself. Kole Roybal and his team are studying how tumors survive, spread, and evade the immune system, then using those insights to design therapies that selectively target cancer cells while sparing healthy tissue.

By combining expertise in genomics, immunology, and synthetic biology, the scientists are developing innovative treatment strategies that make tumors more vulnerable to attacks by the immune system and improve the effectiveness of existing therapies. Their work aims to create more precise, durable cancer treatments that can adapt to the complexity of different tumor types and ultimately improve outcomes for patients.

Vijay Ramani and his group are pushing DNA sequencing and genome-mapping technologies to the next level to reveal cancer biology with unprecedented precision. They are developing advanced single-molecule sequencing approaches to detect rare genetic changes and structural differences in DNA that traditional methods can miss.

More recently, the scientists combined their technology with artificial intelligence, showing that newly copied DNA briefly enters a highly “open” state, giving scientists a new window into how genes are regulated. By generating more accurate and comprehensive genetic information, their work could improve early cancer detection, guide treatment decisions, and help scientists identify new therapeutic opportunities.

A team led by Alex Marson is uncovering how immune cells carefully balance inactive and activated states—a process that is critical for fighting cancer effectively. The scientists identified intricate molecular networks that regulate when immune cells remain at rest, when they launch immune responses, and how key immune genes are turned on or off.

These discoveries provide important insight into how the immune system can be strengthened to recognize and destroy tumors while avoiding harmful overactivation. By mapping the control systems behind immune activity, the researchers hope to identify new therapeutic targets and improve immunotherapies that leverage the body’s natural defenses against cancer.

A group of scientists including Justin Eyquem and Jennifer Doudna are developing new ways to engineer immune cells directly in patients so they can better find and destroy cancer. They engineered novel tools to deliver CRISPR gene editors and synthetic biology tools to generate potent CAR T cell therapies with a single injection. These upgraded immune cells are designed to more accurately target tumors, last longer in the body, and work more safely.

By creating cancer-fighting immune cells directly inside the body—rather than having to extract patient cells, reprogram them in a dish, and infuse them back into the patient— these live-saving therapies are now faster and easier to deliver to patients. The researchers are testing and refining these treatments using lab-grown tumor models with the goal of moving the most effective ones toward clinical use.

In an effort led by Katie Pollard in the Biswas Center for Transformative Computational Cancer Biology, Gladstone researchers are using artificial intelligence and computational biology to better understand and tackle cancer.

They are developing new ways to analyze large and complex biological datasets in order to uncover patterns in how cancer develops and responds to treatment. Their goal is to identify new vulnerabilities in tumors and improve the ability to predict which therapies will be most effective for patients. This work is helping lay the foundation for more data-driven and precise approaches to cancer research and treatment.

Karin Pelka and her team are investigating why immunotherapy works remarkably well for some cancers, but has limited success against many common solid tumors. They are combining next-generation technologies—including organoids, spatial profiling, and artificial intelligence—to understand what tumors actually look like, study how cancer cells interact with other cells in tumors, and figure out how tumors evade detection by the immune system.

The scientists are developing strategies to make immunotherapy more broadly effective, in order to extend the treatment’s benefits beyond a small group of patients and improve treatment options for cancers that are currently difficult to treat.

In the lab of Magnus Hoffmann, scientists are exploring innovative vaccine technologies that train the immune system to recognize and attack cancer cells. Building on advances in virology, immunology, and mRNA-based approaches, they are designing vaccines that stimulate strong and lasting anti-tumor immune responses.

These therapies aim to help the immune system identify unique markers found on cancer cells while sparing healthy tissue. The researchers are also studying how cancer vaccines can work together with other immunotherapies to improve treatment effectiveness. Their goal is to develop safer, more personalized vaccines that prevent cancer recurrence and enhance long-term protection.

Julia Carnevale and Alex Marson are developing new ways to make CAR-T cell therapy more effective against solid tumors, where cancer cells can suppress and block immune responses. Using a genome-wide CRISPR screen in human T cells inside living tumors, the team identified genetic edits to GNAS and P2RY8 that help T cells remain active and better infiltrate tumors. In mouse models, CAR-T cells carrying both edits dramatically improved tumor control, opening new possibilities for next-generation cell therapies for cancers that have been difficult to treat with immunotherapy.

In Matthew Spitzer’s lab, scientists are investigating the complex interactions between cancer and the immune system. They study how cancer alters immune cells throughout the body using advanced single-cell technologies, genomics, and computational tools. By understanding how tumors influence immune responses, their work is helping identify new strategies to improve cancer immunotherapies.

Omar Khan and his team develop innovative approaches to reprogram immune cells using genome editing, epigenetic engineering, and synthetic biology. The researchers are investigating the molecular circuits that control immune cell behavior and designing new tools to precisely direct immune responses. By enhancing the potency, durability, and specificity of engineered immune cells, they aim to advance the next generation of cancer immunotherapies.