Cancer Vaccine to Simultaneously Kill and Prevent Brain Cancer Developed

Summary: A new stem cell therapy approach eliminates established brain tumors and provides long-lasting immunity, training the immune system to prevent the cancer from returning.

Source: Brigham and Women’s Hospital

Scientists use a new way to turn cancer cells into powerful, anti-cancer agents.

In a recent study from Khalid Shah, MS, Ph.D.’s lab at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, researchers have developed a new cell therapy approach to eliminate and induce long-term entrenched tumors. -Sustained immunity, training the immune system so that it can prevent the recurrence of cancer.

The team tested their dual-action cancer-killing vaccine in an advanced mouse model of the deadly brain cancer glioblastoma, with promising results.

The findings were published in: Science Translation Medicine.

MS Ph.D., director of the Center for Stem Cell and Translational Immunotherapy (CSTI). “Our team pursued a simple idea: take cancer cells and turn them into cancer killers and vaccines,” said Khalid Shah. He is vice president of research in the Department of Neurosurgery at Brigham and faculty at Harvard Medical School and the Harvard Stem Cell Institute (HSCI).

“Using gene engineering, we repurpose cancer cells to develop a therapeutic that kills tumor cells and stimulates the immune system to both destroy primary tumors and prevent cancer.”

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Cancer vaccines are an active area of ​​research for many laboratories, but the approach taken by Shah and colleagues is different. Instead of using inactivated tumor cells, the team aims to repurpose live tumor cells with an unusual feature. Like homing pigeons returning to the nest, living tumor cells travel long distances throughout the brain and return to the site of the tumor cells.

Taking advantage of this unique feature, Shah’s team engineered living tumor cells using the gene editing tool CRISPR-Cas9 and reengineered them to release the tumor cell-killing agent.

In addition, engineered tumor cells were engineered to express factors that would make it easier for the immune system to prepare, detect, label, and remember them for a long-term anti-tumor response.

Shows a diagram from this work
Scientists have developed a bifunctional therapeutic strategy by transforming living tumor cells into therapeutics. Shah’s team engineered living tumor cells using the gene editing tool CRISPR-Cas9 and reengineered them to release the tumor cell-killing agent. In addition, engineered tumor cells were engineered to express factors that would make it easier for the immune system to prepare, detect, label, and remember them for a long-term anti-tumor response. The team tested redesigned CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTC) in different strains of mice, including those carrying human-derived bone marrow, liver, and thymus cells that mimic the human immune microenvironment. Shah’s team also built a two-layer security key into the cancer cell that, when activated, destroys ThTCs when needed. Credits: Kok Siong Chen and Khalid Shah.

The team tested redesigned CRISPR-enhanced and reverse-engineered therapeutic tumor cells (ThTC) in different strains of mice, including those carrying human-derived bone marrow, liver, and thymus cells that mimic the human immune microenvironment. Shah’s team also built a two-layer security key into the cancer cell that, when activated, destroys ThTCs when needed.

This dual-action cell therapy was safe, feasible and effective in these models and offers a roadmap for treatment. While further testing and development is needed, Shah’s team specifically chose this model and used human cells to facilitate the path to translate their findings into patient settings.

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“Throughout all the work we do at the center, we never miss the patient, even if it’s highly technical,” Shah said.

“Our goal is to take an innovative but translatable approach so that we can develop a therapeutic, cancer-killing vaccine that will have a lasting impact in medicine.”

Shah and colleagues note that this therapeutic strategy is applicable to a wider range of solid tumors and its applications need to be further investigated.

About this brain cancer research news

Author: press office
Source: Brigham and Women’s Hospital
To contact: Press Office – Brigham and Women’s Hospital
Picture: Image courtesy of Kok Siong Chen and Khalid Shah.

see also

This shows the brain slices

Original research: Open Access.
“Bifunctional cancer cell-based vaccine provides direct tumor killing and antitumor immunity simultaneously” by Kok-Siong Chen et al. Science Translation Medicine


Abstract

Bifunctional cancer cell-based vaccine simultaneously provides direct tumor killing and antitumor immunity

Administration of inactive tumor cells is known to induce a potent antitumor immune response; however, the effectiveness of such an approach is limited by its inability to kill tumor cells before inducing immune responses. Unlike inactivated tumor cells, living tumor cells have the ability to track and target tumors.

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Here, we developed a bifunctional whole cancer cell-based therapeutic with direct tumor-killing and immunostimulating roles. We redesigned tumor cells from resistant interferon-β (IFN-β) using CRISPR-Cas9 by knocking out the IFN-β-specific receptor, and then engineered them to release the immunomodulatory agents IFN-β and granulocyte-macrophage colony-stimulating factor.

These engineered therapeutic tumor cells (ThTCs) abolished glioblastoma tumors established in mice by inducing caspase-mediated cancer cell apoptosis, downregulating cancer-associated fibroblast-expressing platelet-derived growth factor receptor β, and activating antitumor immune cell trafficking and antigen-specific . T cell activation signal.

This mechanism-based efficacy of ThTCs translated into survival benefit and long-term immunity in primary, recurrent and metastatic cancer models in immunocompetent and humanized mice. The inclusion of a double kill switch involving herpes simplex virus-1 thymidine kinase and rapamycin-activated caspase 9 in ThTCs ensured the safety of our approach.

Equipping naturally neoantigen-rich tumor cells with bifunctional therapeutics represents a promising cell-based immunotherapy for solid tumors and provides a roadmap for clinical translation.

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