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Paper Abstract

Is immunotherapy-a ray of hope for diffuse intrinsic pontine glioma patients?

The advent of immunotherapy is a boon to society. It can suppress the immunity escape and reactivate the antitumor activities.

DIPG (diffuse intrinsic pontine glioma), what is it?

DIPG, a type of children's brainstem glioma, a terrifying fatal disease with no treatment to date, is a nightmare to patients. This tumor leads to specific malfunctioning of eyes, ears, and limbs followed by loss of facial sensation along with difficulty in engulfing, opening mouth, and speaking. It significantly affects the patient's quality of life with restricted movement and unwanted home confinement. The DIPG patient’s life becomes miserable with each passing day, and the patient is just left to count the days.

But now there is good news for the DIPG patients, and the patients need not worry like before. Yes because immunotherapy will take care of your body, and you can live life every day. The plight of this disease is beginning to change for patients with the advent of this fantastic immunotherapy intervention.

Thanks to immunotherapy………………………..

Immunotherapy- What is it?

Immunotherapy is a therapy to enhance the body's immune system for anti-cancer activity. The monoclonal antibodies (i.e., antibodies from clonal plasma cells which are successors of single B-cells) and modified T-cells are made within the body of a living organism or in the laboratory respectively, and then injected into the body to modify the immune response and destroy the tumor cells.

Brainstem Glioma.jpg

What’s the immunotherapy treatment for DIPG?

At present, immunotherapy treatments for DIPG include CAR-T-cells (chimeric antigen receptor T-cells), ICIs (immune checkpoint inhibitors), vaccines, and oncolytic viruses.

CAR-T-cells (chimeric antigen receptor T-cells) are a patient’s laboratory-modified T cells to bind to tumor antigens to initiate an immune response and destruct the tumor cells.

ICIs (immune checkpoint inhibitors) are proteins that obstruct the normal immune response from being too aggressive so as to not harm the normal cells when tumor cells liaise with the T-cells while oncolytic viruses are natural or engineered viruses to target tumor cells to efficiently destroy tumor cells without affecting the normal body cells.

Vaccines are the administration of weakened antigens into the body to fight against specified antigens. Cancer vaccine therapy involves boosting foreign antigens, such as tumor-specific DNA and mRNA, to revive the immune system to create an antitumor immune response. However, inadequate attenuated antigens escaping the body's immune system restrict immunotherapy in DIPG.

Presently, the two oncolytic viruses developed for the DIPG treatment are adenovirus DNX-2401 (delta-24-RGD) and herpes simplex virus 1716 (HSV1716), which have been shown to have the potential to target and destroy the tumor cells in laboratory mice models [1].

What other treatments can DIPG patients get and what are they?

DIPG patients can get treatment through clinical trials post-radiation therapy but before and after the tumor progresses.

Diffuse intrinsic pontine glioma or a much-related central nervous system tumor can now get engineered immune cells for treatment.

Many clinical trial patients could not survive the disease complications and only a few experienced significant clinical benefits from the engineered immune cells. In 2017, FDA approved CAR-T (chimeric antigen receptor T-cells) immune-engineered cells for blood cancer treatment, but this technology did not work earlier for brain tumors. Although a complete cure for pediatric brainstem glioma is the need of the hour, CAR-T cell antitumor activity attained in these patients is a remarkable achievement for the entire research team. Patients infused with CAR-T cells into spinal fluid-shrunken brain tumors, relieving symptoms such as difficulty walking and wide mouth opening.

After clinical trial treatment, patients observed the disappearance of their neural problems, although it brings some aspirations in their life for a short time which is truly rewarding. It extends the survival time for patients by several months [2].

CAR-T cell preparation: How is it prepared in the laboratory, and how does it work for brain tumors?

CAR-T cells support our immune cells to enhance the production of efficient killer cells. These CAR-T cells are made by extracting white blood cell (T-cell) samples from the patient's blood and then genetically modified to kill the tumor cells. Researchers in immunotherapy, reveal new exact positions to attack DIPG tumors in lab mice. In a study, the mice models were examined, and the results were found to be encouraging, found that the mice's tumor size reduced or vanished with extended life. Clinical trials (Phase 1) have been going on in the United States, Georgia since 2021 to see the effectiveness of chemo-immunotherapy on pediatric brain cancer patients using drugs like Ibrutinib and Indoximod expected to have promising results from these trials, which might extend the survival of these patients to some extent with better quality of life[3], [1]

However, in spite of all the progress in immunotherapy DIPG remains a deadly and progressive disease that only worsens over time. So DIPG patients should be given every care to improve their lives, and families should be vigilant about the next stages to discuss with the health care team of experts. [4].

References

  1. N. Martínez-Vélezet al., “The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models,” Nat. Commun., vol. 10, no. 1, p. 2235, May 2019, DOI: 10.1038/s41467-019-10043-0.

  2. E. Digitale, “From loss comes hope: Pediatric brain tumor treatment shows promise,” Scope, Feb. 07, 2022. https://scopeblog.stanford.edu/2022/02/07/from-loss-comes-hope-pediatric-brain-tumor-treatment-shows-promise/ (accessed Oct. 05, 2022).

  3. Discovery Points to Better Treatments for Brain Tumors,” UVA Health Newsroom, Jun. 28, 2022. https://newsroom.uvahealth.com/2022/06/28/discovery-points-to-better-treatments-for-brain-tumors/ (accessed Oct. 06, 2022).

  4. G. Giammalvaet al., “End-of-Life Care in High-Grade Glioma Patients. The Palliative and Supportive Perspective,” Brain Sci., vol. 8, no. 7, p. 125, Jun. 2018, DOI: 10.3390/brainsci8070125.

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