I met Sophie Hanina during a department get-together. She was kind, clever, and quite funny. We were talking about the weather, funny reels we’ve seen lately, our experience in the lab, and a gentleman walked into the conference room. “Congratulations on publishing! This is huge!” I felt so goofy for not knowing who I was talking to.
Dr. Sophie Hanina, MD, PhD, is a physician scientist who received her medical degree from the University of Oxford and her doctorate degree from the University of Cambridge. I know right, she is an absolute star.
Her publication, entitled “Sensitive CAR T cells redefine targetable CD70 expression in solid tumors1”, in Science. Science, being one of the most impactful academic publications in the world, is kind of a big deal, and I don’t use that lightly. Usually if an article is accepted into a journal like Science, Nature, Cell, The Lancet, or The New England Journal of Medicine (to name a few), it signals that this work can change the field as we know it.
CAR T cell therapy is a type of immunotherapy where you take a patient's own T cells, genetically engineer them to recognize a specific target on cancer cells, and put them back in to kill the cancerous cells that are growing rapidly and out of control. It's been revolutionary for blood cancers (Dr. Hanina is a hematologist by training) but notoriously difficult to make work in solid tumors, like breast, lung, kidney, and ovarian cancers.
The problem with solid tumors is finding a target that's on the cancer cells but NOT on healthy cells, otherwise the CAR T cells either (1) attack cells non-specifically and cause serious toxicity2 OR they (2) do little to no improvement to minimizing the tumor, and may at best just slow down the progression.
What Dr. Hanina's work does: CD70 is a protein that shows up on certain solid tumors. The issue has always been that CD70 also appears on some healthy tissues, making it a risky target3. Dr. Hanina explained to me that “the work basically uncovers that, what looks negative in the tumor isn’t negative at all, but ultra low, which is where the sensitive receptor comes in. Think of it like a dog whistle. Just because we can’t hear the sound (i.e. the tumor looks negative), doesn’t mean it’s not there. A more sensitive ear, like a dog’s ear, can hear it.” Dog ears in this case are the HIT receptors on the CAR T cells.
Her work on "sensitive" CAR T cells suggests a way to more precisely detect and respond to low CD70 expression levels, essentially making the CAR T cells smart enough to distinguish between how much CD70 is on a cancer cell versus a healthy cell.
The details are a bit complicated, but I think they are definitely worth knowing. This magic that’s researched by so many is happening in our bodies all the time!
Firstly, the team replicated the current standard and efficacy of CAR-T cell therapy for kidney tumors in mice, to confirm that they have a high-throughput model to investigate the “sensitive” CAR-T cells. They then found that alleged CD70-negative tumor cells express more CD70 than tumor cells with CD70 completely knocked out. Interesting, isn’t it?
Now I’ll step back for a second and introduce another protein on the surface of T cells. Human Leukocyte Antigen (HLA), once presented with an antigen by an antigen presenting cell (B cells, macrophages, and others), becomes a T cell that carries a piece of that antigen and knows to target that specific antigen. This is where HLA-Independent T cells (HIT) CAR T cells come into play4. The HLA-restricted part of the protein is instead engineered to be HLA-independent, allowing them to be more specific and avoid the mechanisms of tumor resistance.
These engineered CD70-specific HLA-independent CAR T cells are able to detect the low levels of CD70 in the apparent CD70-negative tumor cells. The low levels of CD70 expression were then found to be the result of epigenetic silencing, not genetic absence. While genetics reflects the actual code of your DNA, epigenetics is the study of how our DNA opens and folds. Open segments of our DNA are turned into RNA and then protein that manifests tangibly in our bodies, while closed segments aren’t transcribed. The epigenetic information we have on patients with solid tumors can be used as target identification.
So the CD70-specific HLA-independent CAR T cells were able to completely eliminate ovarian and pancreatic tumors.
Why this matters: CD70 is expressed in several cancers that disproportionately affect women, including ovarian cancer and cervical cancer.
As someone who studies transplant immunology, where HLA matching is integral to the success of a transplant, or the source of its failure, this work highlights how incredible such a small molecular complex is and how it can change the lives of many.
Dr. Hanina's work reminds us that the most powerful cancer therapies might already exist within us, they just need the right engineer.
1 Sophie A. Hanina, et. al. (2026). Science. Sensitive CAR T cells redefine targetable CD70 expression in solid tumors. https://www.science.org/doi/10.1126/science.adv73.78
2 Jennifer M. Louge, et al. (2022). Blood Advances. Early cytopenias and infections after standard of care idecabtagene vicleucel in relapsed or refractory multiple myeloma. https://ashpublications.org/bloodadvances/article/6/24/6109/486141/Early-cytopenias-and-infections-after-standard-of?guestAccessKey=
3 Jiatao Hu, et al. (2025). Clinical and Translational Medicine. CD70: An emerging target for integrated cancer diagnosis and therapy. https://pmc.ncbi.nlm.nih.gov/articles/PMC12238729/
4 Jorge Mansilla-Soto. (2022). Nature. HLA-independent T cell receptors for targeting tumors with low antigen density. https://www.nature.com/articles/s41591-021-01621-1#:~:text=We%20demonstrate%20that%20these%20HLA%2Dindependent%20T%20cell,high%20antigen%20sensitivity%20and%20mediate%20tumor%20recognition.
Cover Photo by National Cancer Institute on Unsplash