A glimpse into tumor types, advances in diagnoses, and new, promising treatment options with CARv3-TEAM-E T cells based on scientific literature reviews

Photo bythe author citing the paper from the New England Journal of Medicine

This story does not include health advice. It is for information, inspiration, and awareness purposes.

Brain tumors are comprehensive and complex, so covering details in one article is impossible. But when you or someone you love faces this diagnosis, awareness and essential knowledge can go a long way and even might be a lifesaver.

Presenting in four short parts, I have distilled the essential information to give you a solid starting point summarizing vital knowledge to help you understand tumor types, ask the right questions, and have meaningful conversations with your doctors for diagnosis and treatment.

The brain is the most complex organ, managing all other organs. So, the health and disease of the brain can affect our cells, tissues, organs, and systems. I wrote many articles about brain health and risk factors for neurocognitive disorders.

One of the most challenging diseases affecting the brain is the formation of tumors, which are highly complex due to their nature. Understanding these tumors is crucial to finding ways to combat them effectively.

In oncology, various ways are used to diagnose and treat tumors. Some multimodal diagnostic tools are in place. Some scientists are working on universal diagnostic methods. From a treatment angle, surgery, radiation, and chemotherapy help in the short term, but in some cases, tumors eventually return. The recent focus is on immunotherapies.

The study of brain tumors is an active and vibrant field of research with substantial research dollars. As pointed out in this paper, a substantial proportion of brain tumor publications originate from radiology departments, and the percentage of this research that is funded by the NIH has grown significantly.

Advances in genetics and molecular biology are leading to a better understanding of the underlying mechanisms driving tumor growth. This knowledge takes us to more personalized and effective treatments, such as targeted therapies.

I previously touched on immunotherapy in general. However, the most promising and effective immunotherapy is emerging CAR-T Cell therapies, which I want to introduce briefly.

Although CAR-T cell therapy is still new, it shows enormous treatment potential for malignant brain tumors, which I will introduce briefly, linking to credible sources from the growing literature.

A comprehensive 2023 review in Brain Research Bulletin informs that CAR T function has shown limited efficacy against brain tumors due to several factors, including the immunosuppressive tumor microenvironment, blood-brain barrier, and tumor-antigen heterogeneity. Despite these considerations, CAR T-cell therapy has the potential to be implemented as a treatment modality for brain tumors.

Part 1: A Brief Overview of Brain Tumor Types

In this section, without boring you with too much scientific and technical detail, I explain what a brain tumor is, what types of tumors are documented in the literature, and why they matter.

Researchers are exploring innovative treatments such as tumor-treating fields (TTFields), which use electric fields to disrupt cancer cell division. Clinical trials have shown that combining TTFields with traditional therapies can extend patients’ survival.

Brain tumors matter because of their profound impact on our health and quality of life. They present unique challenges due to the brain’s complexity and the critical functions it controls.

A brain tumor is an abnormal growth of cells within the brain or central nervous system. These growths can be benign (non-cancerous) or malignant (cancerous) and vary widely in size, location, and behavior.

Brain tumors can originate in the brain itself (primary brain tumors) or spread to the brain from other parts of the body (secondary or metastatic brain tumors).

Brain tumors are classified based on the type of cell they originate from and their location within the brain. Some common types of brain tumors include Gliomas, Meningiomas, Pituitary Adenomas, Medulloblastomas, and Schwannomas. I’d like to briefly mention their scope.

Gliomas arise from glial cells, which support and protect neurons. Subtypes include astrocytoma, ependymoma, and oligodendroglioma. Glioblastomas grow rapidly and spread aggressively.

As this NIH book informs glioma is the most common form of central nervous system neoplasm that originates from glial cells. In the US, there are six cases of gliomas diagnosed per 100,000 people every year. Gliomas are very diffusely infiltrative tumors that affect the surrounding brain tissue. Glioblastoma is the most malignant type, while pilocytic astrocytomas are the least malignant brain tumors.

The book informs that gliomas (brain tumors) can bring many complications, including increased intracranial pressure, seizures, hydrocephalus, brain herniation, hemorrhage into the tumor, local spread, spinal metastases, and death.

Based on my research, I want to elaborate on gliomas, as the three types (astrocytomas, ependymomas, and oligodendrogliomas) in this category are widespread and have different impacts and implications.

Astrocytomas start in the brain’s support cells called astrocytes. Constituting 60% of brain tumors, glial tumors include astrocytoma as the most prevalent form of glioma. They can be slow-growing or aggressive. Recent studies have identified specific genetic changes that drive these tumors. Understanding these changes allows for more tailored and effective treatments, leading to targeted therapies that can slow tumor progression.

Ependymomas are glial cell tumors that commonly arise in the lining cells of the ventricular system and, less commonly outside, the central nervous system or within the brain parenchyma. They are comprised of genetically distinct subgroups of tumors and affect children more commonly than adults.

Oligodendroglioma is a type of diffusely infiltrating glioma and constitutes approximately 5% of primary intracranial tumors. They usually involve the cortical gray matter and are most commonly seen in the frontal lobes.

An Overview of Other Brain Tumor Types

Medulloblastomas are common brain tumors in children, typically found in the cerebellum, which controls balance and coordination. Advances in genetic profiling have allowed for the classification of medulloblastomas into distinct subgroups, each with unique molecular characteristics.

Meningiomas develop from the meninges, the protective membranes covering the brain and spinal cord. These tumors are usually benign and slow-growing, but their location can lead to significant neurological problems depending on the pressure they exert on the brain or spinal cord.

Pituitary Adenomas are tumors in the pituitary gland, which regulates various hormones in the body. These tumors can cause a range of hormonal imbalances, leading to conditions such as Cushing’s disease or acromegaly. Depending on their size and hormonal activity, treatment options may include surgery, radiation therapy, or medication to control hormone production.

Vestibular Schwannomas arise from Schwann cells, which insulate nerve fibers. These tumors are generally benign but can cause significant problems due to their location along the nerves. Schwannomas most commonly affect the vestibular nerve, leading to hearing loss and balance issues.

Part 2: The Progress in Understanding and Treating Brain Tumors

The progress in understanding brain tumors has been remarkable. Scientists and clinicians are no longer lumping all tumors together but are instead identifying their unique molecular fingerprints.

This detailed knowledge opens doors to personalized treatment, making it possible to tailor therapies to each patient’s specific tumor type. For example, molecular profiling of gliomas can determine if a patient will benefit from drugs targeting the mTOR pathway, offering a more effective and less toxic treatment option.

It was an eye-opener when Nature published a paper this year titled “Deadly brain cancer shrinks after CAR-T therapy — but for how long is unclear.” The paper informed that early studies with engineered immune cells show drastic but often short-lived results in glioblastoma, the most aggressive brain cancer.

Treating brain tumors is challenging because of the need to preserve healthy brain tissue while removing or reducing the tumor. Treatment options include surgery, radiation therapy, chemotherapy, and newer targeted therapies, each with its own set of risks and benefits.

Part 3: Diagnosing Brain Tumors: A Multifaceted Approach

Diagnosing brain tumors is a meticulous process that integrates clinical observation, advanced imaging, tissue analysis, and genetic testing. It begins with a thorough clinical evaluation, where symptoms and medical history are reviewed, followed by a physical examination to detect potential signs such as headaches, seizures, vision or speech changes, and cognitive shifts.

Imaging techniques are crucial in pinpointing the tumor’s location and characteristics. MRI, considered the gold standard, uses powerful magnets and radio waves to create detailed brain images. CT scans provide quick assessments and are particularly useful in emergencies to detect bleeding, swelling, or bone issues. PET scans involve injecting a special dye that distinguishes tumor tissue from normal or scar tissue, offering insights into the tumor’s metabolic activity.

Biopsy methods are essential for definitive diagnosis. Needle biopsy is a minimally invasive procedure guided by imaging, extracting a small tissue sample from the tumor for microscopic analysis to determine its type and aggressiveness. Open biopsy involves surgery to remove part or all of the tumor, enabling a detailed examination of the tumor and surrounding tissue.

Genetic and molecular profiling uses advanced technology to analyze the tumor’s genetic makeup. This approach identifies specific mutations or alterations driving its growth, providing detailed information that enables doctors to tailor treatment plans and explore targeted therapies.

Neurological examinations conducted by neurologists comprehensively assess brain function. This evaluation includes testing reflexes, coordination, senses, and cognitive abilities, which are crucial for pinpointing the tumor’s precise location within the brain and understanding its impact on neurological functions.

In some instances, a lumbar puncture (spinal tap) is performed to collect cerebrospinal fluid (CSF) surrounding the brain and spinal cord. Analyzing the CSF can detect the presence of tumor cells, infection, or other abnormalities, aiding in the diagnostic process and informing treatment decisions.

Part 4: CAR-T Cell Therapy: A Glimmer of Hope

I have been following the research of CAR T-cell therapy since the early 1990s. I first encountered the concept in 1993 through an outstanding paper published in PNAS. It was titled “Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors.”

Over the last 25 years, I have read many papers by oncologists and oncology scientists. The most important milestone in this field from my observations was in 2011 when the New England Journal of Medicine published a clinical trial. The same journal also published another clinical trial in 2013.

In April this year, Frontiers published a comprehensive review covering current clinical studies, results, challenges, and potential strategies for using CAR-T cells in acute myeloid leukemia.

CAR-T cell therapy leverages the power of the patient’s own immune system to fight cancer. It is still in its early stages, but it’s showing real promise, especially for hard-to-treat cancers.

As documented in this Frontiers paper, in its simplest form, CAR structure comprises an antibody or ligand-derived ectodomain fused with a hinge, transmembrane domain and an intracellular T-cell signaling domain.

More specially, CAR-T therapy involves extracting T cells (immune cells) from the patient and re-engineering them in a lab to recognize and destroy cancer cells. These supercharged T cells are then infused back into the patient’s body, where they hunt down and eliminate the tumor cells.

Exploring the potential of CAR-T therapy for brain tumors

Researchers are now exploring the potential of CAR-T therapy for brain tumors. Early studies are encouraging, showing that CAR-T cells can cross the blood-brain barrier and target tumor cells within the brain. For example, a clinical trial at the University of Pennsylvania is investigating CAR-T therapy for glioblastoma, and initial results suggest it may extend survival and improve quality of life.

The progress is inspiring. Scientists and researchers are dedicated to finding solutions, and their efforts are bringing us closer to more effective treatments and, perhaps one day, a cure.

CAR-T cell therapy involves collecting a patient’s T cells through leukapheresis, modifying them in a lab to express chimeric antigen receptors (CARs), multiplying and freezing these cells, and then shipping them back for infusion.

Before infusion, patients may receive conditioning chemotherapy to boost effectiveness. The modified CAR-T cells are infused back into the patient’s bloodstream in a single session, similar to a blood transfusion.

Patients are typically hospitalized for several weeks to monitor side effects closely and must stay near the treatment center for the first 30 days of recovery to address any issues promptly. The total recovery period lasts about three months, during which patients are closely monitored.

Early diagnosis of brain tumors is critical for survival. Therefore, we need to get checked promptly if any symptoms arise. Specialists can diagnose tumors and provide personalized care based on recent scientific advances.

Recent Progress

As featured by the Brain Tumor Charity, Researchers at Mass General Cancer Centre in Massachusetts have started a clinical trial to test CAR-T cell therapy against brain tumors. The phase I trial of INCIPIENT is evaluating the safety of this treatment option for people with newly diagnosed and recurrent glioblastomas — a particularly devastating type of glioma.

As documented in the New England Journal of Medicine in March 2024, early analysis of the first three patients enrolled has shown positive results, with glioblastomas responding to treatment within days of the CAR-T cell infusion.

All patients tolerated the treatment well, which was the most important objective in this early safety trial. Like other CAR-T cell trials, patients experienced fevers after the cells were delivered.

The paper concluded that “Treatment with CARv3-TEAM-E T cells did not result in adverse events greater than grade 3 or dose-limiting toxic effects. Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants.”

Conclusions and Takeaways

While exploring the complexities of brain tumors and the evolving landscape of treatment options, I noticed that the journey toward effective therapies is challenging yet promising.

Brain tumors, with their intricate nature and varied manifestations, necessitate a multifaceted approach to diagnosis and treatment.

Researchers are discovering new possibilities by improving advanced imaging techniques like MRI and PET scans to genetic profiling and innovative therapies such as CAR-T cell therapy that I covered in this post.

While the protective blood-brain barrier and the diverse nature of brain tumors (tumor heterogeneity) still pose significant challenges, advancements in personalized medicine offer hope for more tailored and effective treatments.

My research indicates that early detection remains paramount, highlighting the importance of proactive healthcare and informed decision-making to address neurological and cognitive challenges.

Thank you for reading my perspectives. I wish you a healthy and happy life.

If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.