“For a century we treated cancer by trying to poison it faster than we poisoned the patient. Immunotherapy was the first time we asked the body to do the fighting instead.”
Dr. Carman Giacomantonio, CMO, Sona Nanotech
Every year, a new generation of oncology drugs arrives with promising trial data. Survival curves improve. Headlines follow. And yet, for most patients with most cancers, the immune system, the most sophisticated defense mechanism in the human body, is not part of the treatment plan.
That started to change in the 1990s, and accelerated dramatically in the 2010s. The change had nothing to do with a more powerful poison or a more targeted drug. It had to do with a shift in strategy so fundamental that it earned a Nobel Prize.
Instead of attacking the cancer, researchers figured out how to re-enable the patient.
This article explains that shift: what the immune system is actually doing, why cancer gets around it, and what immunotherapy does differently. It is the foundation for everything else in this series.
What Cancer Actually Is
Think about this. Our bodies are in a constant state of renewal. Cells divide, the old cell dies, and the new cell carries on. That is how we stay alive. That is why the person in the mirror today is not the person in a photograph from twenty years ago. Change is the whole point.
In cancer, something goes wrong with that process. When a cell divides, it is supposed to copy its DNA. Occasionally that copy is imperfect. Broken DNA makes a broken cell. Normally, a broken cell dies. The problem in cancer is that the broken cell does not die. It keeps dividing. And as it does, both the old cell and the new cell compete for space. What they create is a tumor.
Why the Immune System Should Catch It
The immune system is not a passive defense. It is constantly surveilling the body, scanning cells for signs of trouble. The signal it looks for is abnormal protein. When DNA breaks, the protein it encodes breaks too. Any cell carrying abnormal protein is a target.
The key players in that attack are T cells, specifically the cytotoxic T cells that seek out and destroy abnormal cells directly. Natural killer cells play a supporting role, detecting cells that have hidden their surface markers entirely, which is itself a red flag.
This system works. The vast majority of broken cells are found and eliminated before they ever become a tumor. What we call cancer is, in most cases, the minority of cells that managed to get past that surveillance. And understanding how they get past it is the key to understanding why immunotherapy matters.
How Cancer Sends the Wrong Signal
Cancer cells have broken DNA. Broken DNA makes abnormal protein. The immune system sees that abnormal protein and should kill the cell. So far, so good.
Here is where it gets complicated. Many cancer cells also carry surface messages that say, in effect: this is us. These are the same signals that healthy cells use to prevent the immune system from attacking normal tissue. In a cancer cell, those signals are still present, layered on top of the abnormal protein signal.
The immune system is now conflicted. It sees a target, but it also sees a message telling it to stand down. That conflict activates what are called checkpoints, regulatory brakes built into the immune system to stop it from attacking indiscriminately. The cancer has not destroyed the immune system’s ability to see it. It has triggered the immune system’s own off switch.
This is one of the central reasons cancer is so difficult to treat. The tools the immune system needs are intact. The problem is that cancer has learned, through evolutionary pressure, to activate the very mechanisms designed to protect us from our own immune response.
The Shift: Treating the Patient, Not Just the Tumor
For most of oncology’s history, the response to cancer was to try to destroy it directly. Surgery removes it. Radiation burns it. Chemotherapy poisons cells that divide rapidly, and cancer happens to be caught in that crossfire along with hair follicles, gut lining, and bone marrow. Each approach attacks the tumor. Each causes collateral damage to healthy tissue in the process.
The conceptual shift that immunotherapy represents is this: if cancer is evading the immune system by exploiting its own checkpoints, what if the target is not the tumor but the checkpoint itself? What if, instead of attacking the cancer directly, we restore the immune system’s ability to do what it was already trying to do?
That idea is the foundation of modern immunotherapy. Not a more powerful poison. Not a more precise weapon. A different target entirely: the patient’s own defense, re-equipped to finish a fight it was already in the middle of.
The Discovery That Won a Nobel Prize
James Allison, working at what is now the University of Texas MD Anderson Cancer Center, and Tasuku Honjo, working at Kyoto University in Japan, independently spent years studying those immune checkpoints. Both identified specific checkpoint proteins that cancer was exploiting, and both developed antibodies to block them.
Allison targeted CTLA-4, a checkpoint that acts early in the immune response. Honjo identified PD-1 and its binding partner PD-L1, the molecular handshake that tells a T cell to stand down, and which cancer cells display on their surface precisely to trigger that deactivation.
When checkpoint-blocking antibodies were tested in patients with advanced melanoma in the early 2010s, the results were unlike anything the field had seen. Patients with metastatic disease, patients for whom no further options existed, achieved complete responses. Some remained in remission for years. The immune system, once unblocked, could do what no chemotherapy drug had managed.
In 2018, Allison and Honjo received the Nobel Prize in Physiology or Medicine for the discovery of cancer therapy by inhibition of negative immune regulation. It was the field’s formal acknowledgment that treating the immune system had become a pillar of modern oncology.
Why It Still Does Not Work for Most Patients
Checkpoint inhibitors are one of the most significant advances in cancer treatment in decades. For the patients who respond, the benefit can be transformative and durable. That is real, and it matters.
But here is the honest number: in combination, checkpoint inhibitors produce a response in roughly 30 to 50 percent of patients, depending on cancer type. That means 50 to 70 percent of patients do not respond. And among those who do, a significant proportion experience serious side effects from the immune system attacking normal organs, because the checkpoints that were blocking the cancer were also protecting healthy tissue.
The reason most patients do not respond is not that the drugs are weak. The reason is that releasing a checkpoint only helps if the immune system was already activated and engaged with the tumor. In many cancers, it is not. The tumor has done more than activate the immune system’s brakes. It has built an entire environment around itself that keeps the immune system from getting close enough to be braked in the first place.
That is the open problem. It is not a small one. The rest of this series explains what that environment looks like, why it is so effective at excluding the immune system, and what the field is doing to change it.
Sona Nanotech and This Field
Sona Nanotech is a clinical-stage nanobiotechnology company working on exactly this problem. Its published preclinical research explores whether focused, controlled heat delivered inside a tumor can initiate the immune signals that make a cold, immunotherapy-resistant tumor visible to the immune system, and whether that priming can then make checkpoint inhibitors work for patients they currently fail.
Published results in peer-reviewed journals show that in animal models of immunotherapy-resistant cancer, checkpoint inhibitors alone produced no response. Combined with Sona’s targeted heat approach, 100 percent of animals responded.
A first-in-human study in immunotherapy-resistant melanoma has been completed. The manuscript is in preparation.
The next article in this series explains what checkpoint inhibitors are, in plain terms, and why they are not the whole answer.
Sources and Further Reading
- National Cancer Institute. Immunotherapy to Treat Cancer. cancer.gov/about-cancer/treatment/types/immunotherapy
- Cancer Research Institute. What Is Cancer Immunotherapy? cancerresearch.org/immunotherapy/what-is-cancer-immunotherapy
- Society for Immunotherapy of Cancer (SITC). sitcancer.org/immunotherapy
- The Nobel Prize in Physiology or Medicine 2018. James P. Allison and Tasuku Honjo. nobelprize.org/prizes/medicine/2018/summary
- Kennedy BE et al. Targeted intra-tumoral hyperthermia using uniquely biocompatible gold nanorods induces strong immunogenic cell death in two immunogenically ‘cold’ tumor models. Frontiers in Immunology, 2025. DOI: 10.3389/fimmu.2024.1512543
- Kennedy BE et al. Targeted hyperthermia therapy (THT) using gold nanorods remodels the tumor microenvironment to sensitize murine microsatellite-stable colorectal cancer to immune checkpoint blockade. Journal of Nanobiotechnology, 2026. DOI: 10.1186/s12951-026-04310-8