The tumours were turned against themselves
On the Importance of Drug Injection into Tumours for Treatment of Isolated Breast and Lymmas Transplantative Lympoma
Various research groups assess which drug combinations achieve the strongest vaccine responses, with early studies of ISV still in progress. Furthermore, the current need to inject drugs directly into tumours — to avoid dangerously activating the entire immune system — limits which hospitals offer it and precludes treating inaccessible tumours.
Such drug conjugates are being developed. In 2022, Levy and his colleagues completed work that showed that a TLR9-activating drug coupled to a peptide travelled to tumours in mice and shrank these cancers without systemic side effects13. He says it avoids the logistical difficulty of injecting a tumours. So compelling were the results, a start-up company — TwoStep Therapeutics in San Carlos, California — was founded in 2023 to develop such conjugates.
You can see this in how the individual being treated is exposed to a much greater diversity of tumour antigens than the few dozen chosen forpersonalized mRNA vaccines. This could induce a stronger, wider-ranging immune response that powerfully attacks tumours initially and potentially reduces relapses.
He put an immune checkpoint inhibition in mice. The extra element would be the deciding factor in the next trial. Checkpoint inhibitors suppress a mechanism that cancers use to stop T cells attacking them. These drugs have transformed the treatment of several cancer types, although most tumours don’t respond to checkpoint inhibitors alone.
Even though other, more-conventional lymphoma therapies were more effective, it convinced Levy and Brody to continue pursuing ISV. The trial, Brody says, “showed pretty plainly that you can inject something into one tumour and make distant tumours melt away. And some of those remissions were pretty durable.”
The third issue is that these drugs must be delivered directly into tumours to limit systemic toxicity. This makes treatment of tumours like breast cancer and lymphoma more complicated and probably more variable than administering drugs systemically.
She hypothesized that radiation-killed tumour cells sometimes liberate cancer antigens that stimulate the immune system to fight the remaining, metastasized cancer. Demaria thought that she and her team would be able to boost the process if this were true.
Demaria is part of a team that is already exploring this strategy for breast cancer. The trial participants are first given a FLT3 activator and then given a mastectomy to remove their primary tumours. There is a long wait to see if the pre surgical treatment makes a difference in the incidence of post-mastectomy disease. But nearer term, Demaria says that by examining the tissue removed during surgery, she will be able to look for evidence of an active vaccinal process.
By the time Morrison joined a trial in 2017, the approach had grown to include two drugs plus radiation in order to get the key actions on dendritic cells to work.
Morrison had a B-cell Lymphoma that had spread throughout his body after having initial blood tests, scans, and a biopsies. “It just came out of nowhere,” Morrison says.
Turning tumours against yourselves: A case study of Morrison, a New York City lymphoma specialist, as an immunotherapy expert
Second, she says, not knowing which specific antigens are driving immunity makes it difficult to directly test whether ISV induces a T-cell response. The trials will probably take longer without such assays because they need to rely on clinical outcomes and not the development of immunity. Moreover, if clinical benefits are absent, researchers will be uncertain of whether the vaccination failed or whether something downstream prevented tumour regression.
Cancer immunotherapy, in all its variations, is predicated on the immune system’s natural ability to destroy cancerous cells. This happens quite a bit, and is often enough to stop all cancer from developing. There are two ways to escape the immune system when there is a cancer: by preventing it from being recognized or by stopping it from attacking it. Therapeutic cancer vaccines aim to solve the recognition problem.
Morrison was looking for a lymphoma specialist when his son identified the Mount Sinai Hospital in New York City as the one he was looking for. For almost 20 years, Brody has been studying the possibility of vaccinating people who have cancer against their own tumours.
In 2017, Bill Morrison was working hard and feeling fine. But the swelling on his neck was bothering him. “It didn’t hurt but it was kind of puffed out on one side,” he says. It just didn’t seem right.
Source: Turning tumours against themselves
The End of the War: Bringing Back the ‘Ranostics’ to the Care of Isolated Supervised Patients
But, overcoming the challenge of selling this approach to industry partners is arguably the most important next step for ISV to progress towards routine clinical care.
Cancer kills almost ten million people annually. According to a study, this disease will cost the world 25 trillion dollars over the next 30 years, an artificial currency used to compare economies. The JAMA Oncol. 9, 465–474, was published in the year 2023. Fifty years after the US declared war on cancer, many wished the disease would be more defeated than they think it will be. People diagnosed with cancer today often still contend with the dismal side effects and highly uncertain outcomes associated with the decades-old therapeutic gauntlet of radiation, surgery and chemotherapy. New treatments for cancer are arriving quickly and can turn the tide.
By combining medical tasks, theranostics — a combination of therapy and diagnostics — is scoring impressive results. The plan is to get radioactive particles into the body to find cancer and then use different types of radiation to destroy the cancer cells. Researchers are also exploring the use of artificial intelligence to help work out which therapy is best for an individual. With new treatments emerging from labs so rapidly, it might be time to rethink the clinical-trial system lest people be deprived of the most effective treatments available.
We are pleased to say that the financial support of Pfizer in producing this Outlook was acknowledged. As always, Nature retains sole responsibility for all editorial content.
