2025 AACR-CRI Lloyd J. Old Award: Dr. Crystal Mackall Honored for Fearlessly Confronting the “Beast” of Cancer

The Cancer Research Institute (CRI) and the American Association for Cancer Research (AACR) have awarded Dr. Crystal L. Mackall the 2025 AACR-CRI Lloyd J. Old Award in Cancer Immunology, celebrating a career defined by fearless innovation, heartfelt commitment, and life-changing discoveries. With her pioneering work in cancer immunotherapy—particularly her breakthroughs in CAR T-cell therapy for both children and adults—Dr. Mackall has not only transformed the science of cancer treatment, but also brought hope to patients and families facing the unimaginable.

“I have been in this field long enough to know that no one does it alone. I am indebted to so many people that have come before me, that are here with me now and will come after me… I am delighted to carry the torch and do what ever I can for the field,” Dr. Mackall told CRI in an interview ahead of the award presentation on Tuesday, April 29, during AACR’s annual meeting in Chicago.

A physician-scientist guided by empathy and determination, Dr. Mackall serves as the Ernest and Amelia Gallo Family Professor of Pediatrics and Medicine at Stanford University. She is also the Founding Director of the Stanford Center for Cancer Cell Therapy, Associate Director of the Stanford Cancer Institute, and Director of the Parker Institute for Cancer Immunotherapy at Stanford—leadership roles that reflect her unmatched ability to bridge discovery and care.

Driving Innovation in Cancer Immunology

Dr. Mackall’s career has been defined by a singular mission: to turn cutting-edge science into tangible hope. She is a trailblazer in immune cell biology, laying early foundations for the field by identifying the thymus’ essential role in human T cell regeneration and spotlighting interleukin-7 (IL-7) as a key player in T cell homeostasis. These formative insights helped ignite the evolution of immunotherapy.

She later transformed that foundational knowledge into lifesaving therapies. Among the first to demonstrate the success of CD19-targeted CAR T-cell therapy in children with relapsed or treatment-resistant B-cell acute lymphoblastic leukemia, Dr. Mackall gave new options to young patients with none left. She and her team continued to advance the field by developing CD22-targeted CAR T cells for those who no longer responded to CD19 therapy.

Her ambitions didn’t stop with blood cancers. Pushing into the difficult terrain of solid tumors, Dr. Mackall broke new ground with GD2-targeted CAR T-cell therapy for pediatric brain cancers like diffuse intrinsic pontine glioma (DIPG). Her team showed that regional CNS delivery significantly improves outcomes—offering a critical breakthrough in one of oncology’s most challenging frontiers.

“What I saw was just that cancer was such an enigma and such an unmet need in society. There was a need to care for these patients and I just really wanted to go after that beast,” Dr. Mackall told CRI.

Tackling CAR T-Cell Resistance

Even the most powerful therapies can falter. Dr. Mackall’s relentless curiosity has driven her to explore why. She was among the first to identify T cell exhaustion as a key reason some CAR T therapies lose effectiveness over time. Her lab is now pioneering ways to enhance T cell memory and resilience by studying molecular regulators like FOXO1 and mediator kinase.

Her team also uncovered how macrophages—usually helpers in the immune system—can inadvertently eliminate therapeutic T cells. In response, they designed a CD47-based strategy to prevent this, making CAR T therapy not only more powerful, but more precise. “We have literally hundreds of different ways to make cellular therapy smarter, more potent, and even potentially safer because we can regulate them,” said Dr. Mackall.

Pushing Boundaries for the Next Generation

Dr. Mackall continues to break new ground with first-in-human and first-in-child clinical trials that go beyond proving efficacy—they illuminate the inner workings of the immune system. From dendritic cell vaccines and cytokines to NK cells and genetically engineered T cells, her work is driven by a relentless commitment to scientific inquiry and patient impact.

“Those of us who do science are driven by curiosity. You don’t do science because you think there is going to be a paved path for you. You do it because you think you can pave a new path. You need to sell hope and need to make your case,” Dr. Mackall shared.

A Legacy of Hope and Courage

Dr. Crystal Mackall’s legacy is still being written—but its impact is already profound. Through visionary science, deep compassion, and unwavering determination, she has helped redefine what is possible in cancer care. As the 2025 AACR-CRI Lloyd J. Old Award recipient, she stands as a beacon for what the future of medicine can and should be: driven by bold ideas, powered by human empathy, and always focused on curing the incurable.