The new vaccine for brain cancer shows great results in a clinical trial

ScienceAlert

A personalized vaccine for glioblastoma – the most aggressive and fatal type of brain cancer – has extended the survival of four humans in the first clinical trial of its kind.
Equipped with such vital information, the immune system can reprogram the cancer’s defenses and launch a more successful attack.
In the recent clinical trial, four patients with treatment-resistant glioblastoma received either two or four doses of the vaccine.
This early boost to the immune system was also linked to short-term side effects typical of an immune response, like nausea, low fever, and chills, which gradually faded over the next day or two.
The promising results build on a previous trial that tested the vaccine on 10 pet dogs suffering from brain tumors.
One of the trickiest parts about treating glioblastoma tumors is that they are heavily shielded from the immune system.
The tumor microenvironment (TME) is immunosuppressive, which means it causes immune cells to die if they try to attack.
“And the reason we’ve done that in the context of cancer is these clusters alert the immune system in a much more profound way than single particles would.”

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Four people in the first clinical trial of its kind have seen their survival of glioblastoma, the most aggressive and deadly form of brain cancer, extended thanks to a customized vaccine.

The novel medication functions by providing the immune system with a means of ‘identifying’ the tumor and a comprehensive transcriptome “how to handbook.”. This makes known the locations of all the on/off switches for the genes in the tumor.

With this crucial information at its disposal, the immune system can rewire the cancer’s defenses and mount a more potent assault.

Two or four doses of the vaccine were administered to four patients with glioblastoma that was resistant to treatment in the recent clinical trial. Significant and quick immune activation was the outcome of this.

Researchers observed a spike in pro-inflammatory proteins, which are known to attract lethal white blood cells to the area, just hours after the vaccinations were given.

Short-term immune response side effects, such as nausea, a low fever, and chills, were also associated with this early immune system boost. However, these side effects subsided over the course of the following day or two.

According to oncologist and vaccine research pioneer Elias Sayour of the University of Florida, “we could see these tumors shifting from what we refer to as ‘cold’ – immune cold, very few immune cells, very silenced immune response – to ‘hot,’ very active immune response – in less than 48 hours.”.

“Considering how quickly this occurred, that was extremely unexpected. However, it did teach us that we were able to quickly activate the immune system’s early defenses against these cancers, which is essential for triggering the immune response’s later effects. ****.

In the past, individuals with glioblastoma treated with chemotherapy, radiation therapy, and surgery could expect to live for roughly six months, maximum, during which time the disease would not advance.

Two patients had progression-free survival for eight and nine months, respectively, after receiving this new vaccine.

One patient experienced recurrent glioblastoma and lived for an additional nine months. As the first subject in an expanded phase 1 clinical trial, the fourth patient’s exact survival data has not yet been released. When glioblastoma recurs, the median survival is typically five to eight months.

Building on a previous trial in which ten pet dogs with brain tumors were given the vaccine, the encouraging results show promise. Dogs with this terminal diagnosis currently have a median survival rate of 35 days if they receive no further treatment. That figure shot up to 139 days after the vaccination.

Sayour expresses hope that this could lead to a shift in patient care and the development of new platforms for immune system modulation technologies.

The COVID-19 vaccines and the new cancer vaccine share the same underlying technology, although there are some significant distinctions.

Due to their strong immune system shielding, glioblastoma tumors are among the most difficult to treat. Tumor microenvironment (TME) cells are immune-suppressive, meaning that any attempt at attack results in their demise.

By reprogramming the TME with a sample of the tumor, the novel vaccine operates. Researchers can “teach” a patient’s killer immune cells how to bypass the tumor microenvironment (TME) by encapsulating the tumor’s messenger RNA into a deliverable vaccine.

According to Sayour and colleagues, this dual action of the medication enables it to “simultaneously function as vaccines,” alerting the immune system to an intruder, “and as immunomodulating agents,” changing the tumor to make it easier for infection.

“We’re injecting clusters of particles that are wrapping around each other like onions, like a bag full of onions,” says Sayour, as an alternative to injecting single particles.

The rationale behind our actions in the cancer context is that these clusters significantly enhance immune system alertness compared to individual particles. “.

Sayour and his associates are currently attempting to ascertain the best timing, dosage, and combination of treatments to administer in conjunction with the vaccine in order to achieve the best possible outcomes and safety. In order to minimize unfavorable side effects, positive and negative outcomes must be balanced.

Sayour expresses optimism about the potential for this to complement existing immunotherapies and even open doors for them.

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